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39 * \brief Implementation of the Weighted Histogram Analysis Method (WHAM)
41 * \author Jochen Hub <jhub@gwdg.de>
57 #include "gromacs/commandline/pargs.h"
58 #include "gromacs/fileio/tpxio.h"
59 #include "gromacs/fileio/xvgr.h"
60 #include "gromacs/gmxana/gmx_ana.h"
61 #include "gromacs/math/functions.h"
62 #include "gromacs/math/units.h"
63 #include "gromacs/math/vec.h"
64 #include "gromacs/mdtypes/inputrec.h"
65 #include "gromacs/mdtypes/md_enums.h"
66 #include "gromacs/mdtypes/pull-params.h"
67 #include "gromacs/mdtypes/state.h"
68 #include "gromacs/pulling/pull.h"
69 #include "gromacs/random/tabulatednormaldistribution.h"
70 #include "gromacs/random/threefry.h"
71 #include "gromacs/random/uniformintdistribution.h"
72 #include "gromacs/random/uniformrealdistribution.h"
73 #include "gromacs/utility/arraysize.h"
74 #include "gromacs/utility/cstringutil.h"
75 #include "gromacs/utility/exceptions.h"
76 #include "gromacs/utility/fatalerror.h"
77 #include "gromacs/utility/futil.h"
78 #include "gromacs/utility/gmxomp.h"
79 #include "gromacs/utility/pleasecite.h"
80 #include "gromacs/utility/smalloc.h"
82 //! longest file names allowed in input files
83 #define WHAM_MAXFILELEN 2048
86 * enum for energy units
89 enSel, en_kJ, en_kCal, en_kT, enNr
92 * enum for type of input files (pdos, tpr, or pullf)
95 whamin_unknown, whamin_tpr, whamin_pullxf, whamin_pdo
98 /*! \brief enum for bootstrapping method
100 * These bootstrap methods are supported:
101 * - bootstrap complete histograms with continuous weights (Bayesian bootstrap)
102 * (bsMethod_BayesianHist)
103 * - bootstrap complete histograms (bsMethod_hist)
104 * - bootstrap trajectories from given umbrella histograms. This generates new
105 * "synthetic" histograms (bsMethod_traj)
106 * - bootstrap trajectories from Gaussian with mu/sigma computed from
107 * the respective histogram (bsMethod_trajGauss). This gives very similar
108 * results compared to bsMethod_traj.
110 * ********************************************************************
111 * FOR MORE DETAILS ON THE BOOTSTRAP METHODS (INCLUDING EXAMPLES), SEE
112 * JS Hub, BL de Groot, D van der Spoel
113 * g_wham - A free weighted histogram analysis implementation including
114 * robust error and autocorrelation estimates,
115 * J Chem Theory Comput, 6(12), 3713-3720 (2010)
116 * ********************************************************************
119 bsMethod_unknown, bsMethod_BayesianHist, bsMethod_hist,
120 bsMethod_traj, bsMethod_trajGauss
123 //! Parameters of one pull coodinate
126 int pull_type; //!< such as constraint, umbrella, ...
127 int geometry; //!< such as distance, direction, cylinder
128 int ngroup; //!< the number of pull groups involved
129 ivec dim; //!< pull dimension with geometry distance
130 int ndim; //!< nr of pull_dim != 0
131 real k; //!< force constants in tpr file
132 real init_dist; //!< reference displacement
133 char coord_unit[256]; //!< unit of the displacement
136 //! Parameters of the umbrella potentials
140 * \name Using umbrella pull code since gromacs 4.x
143 int npullcrds; //!< nr of umbrella pull coordinates for reading
144 t_pullcoord *pcrd; //!< the pull coordinates
145 gmx_bool bPrintCOM; //!< COMs of pull groups writtn in pullx.xvg
146 gmx_bool bPrintRefValue; //!< Reference value for the coordinate written in pullx.xvg
147 gmx_bool bPrintComp; //!< Components of pull distance written to pullx.xvg ?
151 * \name Using PDO files common until gromacs 3.x
159 char PullName[4][256];
161 double UmbCons[4][3];
165 //! Data in the umbrella histograms
168 int nPull; //!< nr of pull groups in this pdo or pullf/x file
169 double **Histo; //!< nPull histograms
170 double **cum; //!< nPull cumulative distribution functions
171 int nBin; //!< nr of bins. identical to opt->bins
172 double *k; //!< force constants for the nPull coords
173 double *pos; //!< umbrella positions for the nPull coords
174 double *z; //!< z=(-Fi/kT) for the nPull coords. These values are iteratively computed during wham
175 int *N; //!< nr of data points in nPull histograms.
176 int *Ntot; //!< also nr of data points. N and Ntot only differ if bHistEq==TRUE
178 /*! \brief g = 1 + 2*tau[int]/dt where tau is the integrated autocorrelation time.
180 * Compare, e.g. Ferrenberg/Swendsen, PRL 63:1195 (1989),
181 * Kumar et al, J Comp Chem 13, 1011-1021 (1992), eq. 28
184 double *tau; //!< intetrated autocorrelation time (IACT)
185 double *tausmooth; //!< smoothed IACT
187 double dt; //!< timestep in the input data. Can be adapted with gmx wham option -dt
189 /*! \brief TRUE, if any data point of the histogram is within min and max, otherwise FALSE */
191 real **ztime; //!< input data z(t) as a function of time. Required to compute ACTs
193 /*! \brief average force estimated from average displacement, fAv=dzAv*k
195 * Used for integration to guess the potential.
198 real *aver; //!< average of histograms
199 real *sigma; //!< stddev of histograms
200 double *bsWeight; //!< for bootstrapping complete histograms with continuous weights
203 //! Selection of pull coordinates to be used in WHAM (one structure for each tpr file)
206 int n; //!< total nr of pull coords in this tpr file
207 int nUse; //!< nr of pull coords used
208 gmx_bool *bUse; //!< boolean array of size n. =1 if used, =0 if not
211 //! Parameters of WHAM
212 typedef struct // NOLINT(clang-analyzer-optin.performance.Padding)
218 const char *fnTpr, *fnPullf, *fnCoordSel;
219 const char *fnPdo, *fnPullx; //!< file names of input
220 gmx_bool bTpr, bPullf, bPdo, bPullx; //!< input file types given?
221 real tmin, tmax, dt; //!< only read input within tmin and tmax with dt
223 gmx_bool bInitPotByIntegration; //!< before WHAM, guess potential by force integration. Yields 1.5 to 2 times faster convergence
224 int stepUpdateContrib; //!< update contribution table every ... iterations. Accelerates WHAM.
225 int nCoordsel; //!< if >0: use only certain group in WHAM, if ==0: use all groups
226 t_coordselection *coordsel; //!< for each tpr file: which pull coordinates to use in WHAM?
229 * \name Basic WHAM options
232 int bins; //!< nr of bins, min, max, and dz of profile
234 real Temperature, Tolerance; //!< temperature, converged when probability changes less than Tolerance
235 gmx_bool bCycl; //!< generate cyclic (periodic) PMF
238 * \name Output control
241 gmx_bool bLog; //!< energy output (instead of probability) for profile
242 int unit; //!< unit for PMF output kJ/mol or kT or kCal/mol
243 gmx_bool bSym; //!< symmetrize PMF around z=0 after WHAM, useful for membranes etc.
244 /*! \brief after wham, set prof to zero at this z-position.
245 * When bootstrapping, set zProf0 to a "stable" reference position.
248 gmx_bool bProf0Set; //!< setting profile to 0 at zProf0?
250 gmx_bool bBoundsOnly, bHistOnly; //!< determine min and max, or write histograms and exit
251 gmx_bool bAuto; //!< determine min and max automatically but do not exit
253 gmx_bool verbose; //!< more noisy wham mode
254 int stepchange; //!< print maximum change in prof after how many interations
255 gmx_output_env_t *oenv; //!< xvgr options
258 * \name Autocorrelation stuff
261 gmx_bool bTauIntGiven, bCalcTauInt; //!< IACT given or should be calculated?
262 real sigSmoothIact; //!< sigma of Gaussian to smooth ACTs
263 gmx_bool bAllowReduceIact; //!< Allow to reduce ACTs during smoothing. Otherwise ACT are only increased during smoothing
264 real acTrestart; //!< when computing ACT, time between restarting points
266 /* \brief Enforce the same weight for each umbella window, that is
267 * calculate with the same number of data points for
268 * each window. That can be reasonable, if the histograms
269 * have different length, but due to autocorrelation,
270 * a longer simulation should not have larger weightin wham.
276 * \name Bootstrapping stuff
279 int nBootStrap; //!< nr of bootstraps (50 is usually enough)
281 /* \brief bootstrap method
283 * if == bsMethod_hist, consider complete histograms as independent
284 * data points and, hence, only mix complete histograms.
285 * if == bsMethod_BayesianHist, consider complete histograms
286 * as independent data points, but assign random weights
287 * to the histograms during the bootstrapping ("Bayesian bootstrap")
288 * In case of long correlations (e.g., inside a channel), these
289 * will yield a more realistic error.
290 * if == bsMethod_traj(Gauss), generate synthetic histograms
292 * histogram by generating an autocorrelated random sequence
293 * that is distributed according to the respective given
294 * histogram. With bsMethod_trajGauss, bootstrap from a Gaussian
295 * (instead of from the umbrella histogram) to generate a new
300 /* \brief autocorrelation time (ACT) used to generate synthetic histograms. If ==0, use calculated ACF */
303 /* \brief when mixing histograms, mix only histograms withing blocks
304 long the reaction coordinate xi. Avoids gaps along xi. */
305 int histBootStrapBlockLength;
307 int bsSeed; //!< random seed for bootstrapping
309 /* \brief Write cumulative distribution functions (CDFs) of histograms
310 and write the generated histograms for each bootstrap */
314 * \name tabulated umbrella potential stuff
318 double *tabX, *tabY, tabMin, tabMax, tabDz;
321 gmx::DefaultRandomEngine rng; //!< gromacs random number generator
322 gmx::TabulatedNormalDistribution<> normalDistribution; //!< Uses default: real output, 14-bit table
325 //! Make an umbrella window (may contain several histograms)
326 static t_UmbrellaWindow * initUmbrellaWindows(int nwin)
328 t_UmbrellaWindow *win;
331 for (i = 0; i < nwin; i++)
333 win[i].Histo = win[i].cum = nullptr;
334 win[i].k = win[i].pos = win[i].z = nullptr;
335 win[i].N = win[i].Ntot = nullptr;
336 win[i].g = win[i].tau = win[i].tausmooth = nullptr;
337 win[i].bContrib = nullptr;
338 win[i].ztime = nullptr;
339 win[i].forceAv = nullptr;
340 win[i].aver = win[i].sigma = nullptr;
341 win[i].bsWeight = nullptr;
346 //! Delete an umbrella window (may contain several histograms)
347 static void freeUmbrellaWindows(t_UmbrellaWindow *win, int nwin)
350 for (i = 0; i < nwin; i++)
354 for (j = 0; j < win[i].nPull; j++)
356 sfree(win[i].Histo[j]);
361 for (j = 0; j < win[i].nPull; j++)
363 sfree(win[i].cum[j]);
368 for (j = 0; j < win[i].nPull; j++)
370 sfree(win[i].bContrib[j]);
382 sfree(win[i].tausmooth);
383 sfree(win[i].bContrib);
385 sfree(win[i].forceAv);
388 sfree(win[i].bsWeight);
394 * Read and setup tabulated umbrella potential
396 static void setup_tab(const char *fn, t_UmbrellaOptions *opt)
401 printf("Setting up tabulated potential from file %s\n", fn);
402 nl = read_xvg(fn, &y, &ny);
406 gmx_fatal(FARGS, "Found %d columns in %s. Expected 2.\n", ny, fn);
408 opt->tabMin = y[0][0];
409 opt->tabMax = y[0][nl-1];
410 opt->tabDz = (opt->tabMax-opt->tabMin)/(nl-1);
413 gmx_fatal(FARGS, "The tabulated potential in %s must be provided in \n"
414 "ascending z-direction", fn);
416 for (i = 0; i < nl-1; i++)
418 if (std::abs(y[0][i+1]-y[0][i]-opt->tabDz) > opt->tabDz/1e6)
420 gmx_fatal(FARGS, "z-values in %d are not equally spaced.\n", ny, fn);
425 for (i = 0; i < nl; i++)
427 opt->tabX[i] = y[0][i];
428 opt->tabY[i] = y[1][i];
430 printf("Found equally spaced tabulated potential from %g to %g, spacing %g\n",
431 opt->tabMin, opt->tabMax, opt->tabDz);
434 //! Read the header of an PDO file (position, force const, nr of groups)
435 static void read_pdo_header(FILE * file, t_UmbrellaHeader * header, t_UmbrellaOptions *opt)
438 char Buffer0[256], Buffer1[256], Buffer2[256], Buffer3[256], Buffer4[256];
440 std::istringstream ist;
443 if (fgets(line, 2048, file) == nullptr)
445 gmx_fatal(FARGS, "Error reading header from pdo file\n");
448 ist >> Buffer0 >> Buffer1 >> Buffer2;
449 if (std::strcmp(Buffer1, "UMBRELLA") != 0)
451 gmx_fatal(FARGS, "This does not appear to be a valid pdo file. Found %s, expected %s\n"
452 "(Found in first line: `%s')\n",
453 Buffer1, "UMBRELLA", line);
455 if (std::strcmp(Buffer2, "3.0") != 0)
457 gmx_fatal(FARGS, "This does not appear to be a version 3.0 pdo file");
461 if (fgets(line, 2048, file) == nullptr)
463 gmx_fatal(FARGS, "Error reading header from pdo file\n");
466 ist >> Buffer0 >> Buffer1 >> Buffer2 >> header->Dims[0] >> header->Dims[1] >> header->Dims[2];
467 /* printf("%d %d %d\n", header->Dims[0],header->Dims[1],header->Dims[2]); */
469 header->nDim = header->Dims[0] + header->Dims[1] + header->Dims[2];
470 if (header->nDim != 1)
472 gmx_fatal(FARGS, "Currently only supports one dimension");
476 if (fgets(line, 2048, file) == nullptr)
478 gmx_fatal(FARGS, "Error reading header from pdo file\n");
481 ist >> Buffer0 >> Buffer1 >> header->nSkip;
484 if (fgets(line, 2048, file) == nullptr)
486 gmx_fatal(FARGS, "Error reading header from pdo file\n");
489 ist >> Buffer0 >> Buffer1 >> Buffer2 >> header->Reference;
492 if (fgets(line, 2048, file) == nullptr)
494 gmx_fatal(FARGS, "Error reading header from pdo file\n");
497 ist >> Buffer0 >> Buffer1 >> Buffer2 >> Buffer3 >> Buffer4 >> header->nPull;
501 printf("\tFound nPull=%d , nSkip=%d, ref=%s\n", header->nPull, header->nSkip,
505 for (i = 0; i < header->nPull; ++i)
507 if (fgets(line, 2048, file) == nullptr)
509 gmx_fatal(FARGS, "Error reading header from pdo file\n");
512 ist >> Buffer0 >> Buffer1 >> Buffer2 >> header->PullName[i];
513 ist >> Buffer0 >> Buffer1 >> header->UmbPos[i][0];
514 ist >> Buffer0 >> Buffer1 >> header->UmbCons[i][0];
518 printf("\tpullgroup %d, pullname = %s, UmbPos = %g, UmbConst = %g\n",
519 i, header->PullName[i], header->UmbPos[i][0], header->UmbCons[i][0]);
523 if (fgets(line, 2048, file) == nullptr)
525 gmx_fatal(FARGS, "Cannot read from file\n");
529 if (std::strcmp(Buffer3, "#####") != 0)
531 gmx_fatal(FARGS, "Expected '#####', found %s. Hick.\n", Buffer3);
536 static char *fgets3(FILE *fp, char ptr[], int *len)
541 if (fgets(ptr, *len-1, fp) == nullptr)
546 while ((std::strchr(ptr, '\n') == nullptr) && (!feof(fp)))
548 /* This line is longer than len characters, let's increase len! */
552 if (fgets(p-1, STRLEN, fp) == nullptr)
557 slen = std::strlen(ptr);
558 if (ptr[slen-1] == '\n')
566 /*! \brief Read the data columns of and PDO file.
568 * TO DO: Get rid of the scanf function to avoid the clang warning.
569 * At the moment, this warning is avoided by hiding the format string
570 * the variable fmtlf.
572 static void read_pdo_data(FILE * file, t_UmbrellaHeader * header,
573 int fileno, t_UmbrellaWindow * win,
574 t_UmbrellaOptions *opt,
575 gmx_bool bGetMinMax, real *mintmp, real *maxtmp)
577 int i, inttemp, bins, count, ntot;
578 real minval, maxval, minfound = 1e20, maxfound = -1e20;
579 double temp, time, time0 = 0, dt;
581 t_UmbrellaWindow * window = nullptr;
582 gmx_bool timeok, dt_ok = true;
583 char *tmpbuf = nullptr, fmt[256], fmtign[256], fmtlf[5] = "%lf";
584 int len = STRLEN, dstep = 1;
585 const int blocklen = 4096;
586 int *lennow = nullptr;
595 /* Need to alocate memory and set up structure */
596 window->nPull = header->nPull;
599 snew(window->Histo, window->nPull);
600 snew(window->z, window->nPull);
601 snew(window->k, window->nPull);
602 snew(window->pos, window->nPull);
603 snew(window->N, window->nPull);
604 snew(window->Ntot, window->nPull);
605 snew(window->g, window->nPull);
606 snew(window->bsWeight, window->nPull);
608 window->bContrib = nullptr;
610 if (opt->bCalcTauInt)
612 snew(window->ztime, window->nPull);
616 window->ztime = nullptr;
618 snew(lennow, window->nPull);
620 for (i = 0; i < window->nPull; ++i)
623 window->bsWeight[i] = 1.;
624 snew(window->Histo[i], bins);
625 window->k[i] = header->UmbCons[i][0];
626 window->pos[i] = header->UmbPos[i][0];
630 if (opt->bCalcTauInt)
632 window->ztime[i] = nullptr;
636 /* Done with setup */
642 minval = maxval = bins = 0; /* Get rid of warnings */
647 while ( (ptr = fgets3(file, tmpbuf, &len)) != nullptr)
651 if (ptr[0] == '#' || std::strlen(ptr) < 2)
656 /* Initiate format string */
658 std::strcat(fmtign, "%*s");
660 sscanf(ptr, fmtlf, &time); /* printf("Time %f\n",time); */
661 /* Round time to fs */
662 time = 1.0/1000*( gmx::roundToInt64(time*1000) );
664 /* get time step of pdo file */
674 dstep = gmx::roundToInt(opt->dt/dt);
682 window->dt = dt*dstep;
687 dt_ok = ((count-1)%dstep == 0);
688 timeok = (dt_ok && time >= opt->tmin && time <= opt->tmax);
690 printf(" time = %f, (tmin,tmax)=(%e,%e), dt_ok=%d timeok=%d\n",
691 time,opt->tmin, opt->tmax, dt_ok,timeok); */
695 for (i = 0; i < header->nPull; ++i)
697 std::strcpy(fmt, fmtign);
698 std::strcat(fmt, "%lf"); /* Creating a format stings such as "%*s...%*s%lf" */
699 std::strcat(fmtign, "%*s"); /* ignoring one more entry in the next loop */
700 if (sscanf(ptr, fmt, &temp))
702 temp += header->UmbPos[i][0];
716 if (opt->bCalcTauInt)
718 /* save time series for autocorrelation analysis */
719 ntot = window->Ntot[i];
720 if (ntot >= lennow[i])
722 lennow[i] += blocklen;
723 srenew(window->ztime[i], lennow[i]);
725 window->ztime[i][ntot] = temp;
729 temp /= (maxval-minval);
731 temp = std::floor(temp);
733 inttemp = static_cast<int> (temp);
740 else if (inttemp >= bins)
746 if (inttemp >= 0 && inttemp < bins)
748 window->Histo[i][inttemp] += 1.;
756 if (time > opt->tmax)
760 printf("time %f larger than tmax %f, stop reading pdo file\n", time, opt->tmax);
776 /*! \brief Set identical weights for all histograms
778 * Normally, the weight is given by the number data points in each
779 * histogram, together with the autocorrelation time. This can be overwritten
780 * by this routine (not recommended). Since we now support autocorrelations, it is better to set
781 * an appropriate autocorrelation times instead of using this function.
783 static void enforceEqualWeights(t_UmbrellaWindow * window, int nWindows)
785 int i, k, j, NEnforced;
788 NEnforced = window[0].Ntot[0];
789 printf("\nFound -hist-eq. Enforcing equal weights for all histograms, \ni.e. doing a "
790 "non-weighted histogram analysis method. Ndata = %d\n", NEnforced);
791 /* enforce all histograms to have the same weight as the very first histogram */
793 for (j = 0; j < nWindows; ++j)
795 for (k = 0; k < window[j].nPull; ++k)
797 ratio = 1.0*NEnforced/window[j].Ntot[k];
798 for (i = 0; i < window[0].nBin; ++i)
800 window[j].Histo[k][i] *= ratio;
802 window[j].N[k] = gmx::roundToInt(ratio*window[j].N[k]);
807 /*! \brief Simple linear interpolation between two given tabulated points
809 static double tabulated_pot(double dist, t_UmbrellaOptions *opt)
812 double pl, pu, dz, dp;
814 jl = static_cast<int> (std::floor((dist-opt->tabMin)/opt->tabDz));
816 if (jl < 0 || ju >= opt->tabNbins)
818 gmx_fatal(FARGS, "Distance %f out of bounds of tabulated potential (jl=%d, ju=%d).\n"
819 "Provide an extended table.", dist, jl, ju);
823 dz = dist-opt->tabX[jl];
824 dp = (pu-pl)*dz/opt->tabDz;
830 * Check which bins substiantially contribute (accelerates WHAM)
832 * Don't worry, that routine does not mean we compute the PMF in limited precision.
833 * After rapid convergence (using only substiantal contributions), we always switch to
836 static void setup_acc_wham(const double *profile, t_UmbrellaWindow * window, int nWindows,
837 t_UmbrellaOptions *opt)
839 int i, j, k, nGrptot = 0, nContrib = 0, nTot = 0;
840 double U, min = opt->min, dz = opt->dz, temp, ztot_half, distance, ztot, contrib1, contrib2;
841 gmx_bool bAnyContrib;
842 static int bFirst = 1;
843 static double wham_contrib_lim;
847 for (i = 0; i < nWindows; ++i)
849 nGrptot += window[i].nPull;
851 wham_contrib_lim = opt->Tolerance/nGrptot;
854 ztot = opt->max-opt->min;
857 for (i = 0; i < nWindows; ++i)
859 if (!window[i].bContrib)
861 snew(window[i].bContrib, window[i].nPull);
863 for (j = 0; j < window[i].nPull; ++j)
865 if (!window[i].bContrib[j])
867 snew(window[i].bContrib[j], opt->bins);
870 for (k = 0; k < opt->bins; ++k)
872 temp = (1.0*k+0.5)*dz+min;
873 distance = temp - window[i].pos[j]; /* distance to umbrella center */
875 { /* in cyclic wham: */
876 if (distance > ztot_half) /* |distance| < ztot_half */
880 else if (distance < -ztot_half)
885 /* Note: there are two contributions to bin k in the wham equations:
886 i) N[j]*exp(- U/(BOLTZ*opt->Temperature) + window[i].z[j])
887 ii) exp(- U/(BOLTZ*opt->Temperature))
888 where U is the umbrella potential
889 If any of these number is larger wham_contrib_lim, I set contrib=TRUE
894 U = 0.5*window[i].k[j]*gmx::square(distance); /* harmonic potential assumed. */
898 U = tabulated_pot(distance, opt); /* Use tabulated potential */
900 contrib1 = profile[k]*std::exp(-U/(BOLTZ*opt->Temperature));
901 contrib2 = window[i].N[j]*std::exp(-U/(BOLTZ*opt->Temperature) + window[i].z[j]);
902 window[i].bContrib[j][k] = (contrib1 > wham_contrib_lim || contrib2 > wham_contrib_lim);
903 bAnyContrib = bAnyContrib || window[i].bContrib[j][k];
904 if (window[i].bContrib[j][k])
910 /* If this histo is far outside min and max all bContrib may be FALSE,
911 causing a floating point exception later on. To avoid that, switch
915 for (k = 0; k < opt->bins; ++k)
917 window[i].bContrib[j][k] = TRUE;
924 printf("Initialized rapid wham stuff (contrib tolerance %g)\n"
925 "Evaluating only %d of %d expressions.\n\n", wham_contrib_lim, nContrib, nTot);
930 printf("Updated rapid wham stuff. (evaluating only %d of %d contributions)\n",
936 //! Compute the PMF (one of the two main WHAM routines)
937 static void calc_profile(double *profile, t_UmbrellaWindow * window, int nWindows,
938 t_UmbrellaOptions *opt, gmx_bool bExact)
940 double ztot_half, ztot, min = opt->min, dz = opt->dz;
942 ztot = opt->max-opt->min;
949 int nthreads = gmx_omp_get_max_threads();
950 int thread_id = gmx_omp_get_thread_num();
952 int i0 = thread_id*opt->bins/nthreads;
953 int i1 = std::min(opt->bins, ((thread_id+1)*opt->bins)/nthreads);
955 for (i = i0; i < i1; ++i)
958 double num, denom, invg, temp = 0, distance, U = 0;
960 for (j = 0; j < nWindows; ++j)
962 for (k = 0; k < window[j].nPull; ++k)
964 invg = 1.0/window[j].g[k] * window[j].bsWeight[k];
965 temp = (1.0*i+0.5)*dz+min;
966 num += invg*window[j].Histo[k][i];
968 if (!(bExact || window[j].bContrib[k][i]))
972 distance = temp - window[j].pos[k]; /* distance to umbrella center */
974 { /* in cyclic wham: */
975 if (distance > ztot_half) /* |distance| < ztot_half */
979 else if (distance < -ztot_half)
987 U = 0.5*window[j].k[k]*gmx::square(distance); /* harmonic potential assumed. */
991 U = tabulated_pot(distance, opt); /* Use tabulated potential */
993 denom += invg*window[j].N[k]*std::exp(-U/(BOLTZ*opt->Temperature) + window[j].z[k]);
996 profile[i] = num/denom;
999 GMX_CATCH_ALL_AND_EXIT_WITH_FATAL_ERROR;
1003 //! Compute the free energy offsets z (one of the two main WHAM routines)
1004 static double calc_z(const double * profile, t_UmbrellaWindow * window, int nWindows,
1005 t_UmbrellaOptions *opt, gmx_bool bExact)
1007 double min = opt->min, dz = opt->dz, ztot_half, ztot;
1008 double maxglob = -1e20;
1010 ztot = opt->max-opt->min;
1013 #pragma omp parallel
1017 int nthreads = gmx_omp_get_max_threads();
1018 int thread_id = gmx_omp_get_thread_num();
1020 int i0 = thread_id*nWindows/nthreads;
1021 int i1 = std::min(nWindows, ((thread_id+1)*nWindows)/nthreads);
1022 double maxloc = -1e20;
1024 for (i = i0; i < i1; ++i)
1026 double total = 0, temp, distance, U = 0;
1029 for (j = 0; j < window[i].nPull; ++j)
1032 for (k = 0; k < window[i].nBin; ++k)
1034 if (!(bExact || window[i].bContrib[j][k]))
1038 temp = (1.0*k+0.5)*dz+min;
1039 distance = temp - window[i].pos[j]; /* distance to umbrella center */
1041 { /* in cyclic wham: */
1042 if (distance > ztot_half) /* |distance| < ztot_half */
1046 else if (distance < -ztot_half)
1054 U = 0.5*window[i].k[j]*gmx::square(distance); /* harmonic potential assumed. */
1058 U = tabulated_pot(distance, opt); /* Use tabulated potential */
1060 total += profile[k]*std::exp(-U/(BOLTZ*opt->Temperature));
1062 /* Avoid floating point exception if window is far outside min and max */
1065 total = -std::log(total);
1071 temp = std::abs(total - window[i].z[j]);
1076 window[i].z[j] = total;
1079 /* Now get maximum maxloc from the threads and put in maxglob */
1080 if (maxloc > maxglob)
1082 #pragma omp critical
1084 if (maxloc > maxglob)
1091 GMX_CATCH_ALL_AND_EXIT_WITH_FATAL_ERROR;
1097 //! Make PMF symmetric around 0 (useful e.g. for membranes)
1098 static void symmetrizeProfile(double* profile, t_UmbrellaOptions *opt)
1100 int i, j, bins = opt->bins;
1101 double *prof2, min = opt->min, max = opt->max, dz = opt->dz, zsym, deltaz, profsym;
1104 if (min > 0. || max < 0.)
1106 gmx_fatal(FARGS, "Cannot symmetrize profile around z=0 with min=%f and max=%f\n",
1107 opt->min, opt->max);
1112 for (i = 0; i < bins; i++)
1116 /* bin left of zsym */
1117 j = gmx::roundToInt((zsym-min)/dz)-1;
1118 if (j >= 0 && (j+1) < bins)
1120 /* interpolate profile linearly between bins j and j+1 */
1121 z1 = min+(j+0.5)*dz;
1123 profsym = profile[j] + (profile[j+1]-profile[j])/dz*deltaz;
1124 /* average between left and right */
1125 prof2[i] = 0.5*(profsym+profile[i]);
1129 prof2[i] = profile[i];
1133 std::memcpy(profile, prof2, bins*sizeof(double));
1137 //! Set energy unit (kJ/mol,kT,kCal/mol) and set it to zero at opt->zProf0
1138 static void prof_normalization_and_unit(double * profile, t_UmbrellaOptions *opt)
1141 double unit_factor = 1., diff;
1145 /* Not log? Nothing to do! */
1151 /* Get profile in units of kT, kJ/mol, or kCal/mol */
1152 if (opt->unit == en_kT)
1156 else if (opt->unit == en_kJ)
1158 unit_factor = BOLTZ*opt->Temperature;
1160 else if (opt->unit == en_kCal)
1162 unit_factor = (BOLTZ/CAL2JOULE)*opt->Temperature;
1166 gmx_fatal(FARGS, "Sorry, I don't know this energy unit.");
1169 for (i = 0; i < bins; i++)
1171 if (profile[i] > 0.0)
1173 profile[i] = -std::log(profile[i])*unit_factor;
1177 /* shift to zero at z=opt->zProf0 */
1178 if (!opt->bProf0Set)
1184 /* Get bin with shortest distance to opt->zProf0
1185 (-0.5 from bin position and +0.5 from rounding cancel) */
1186 imin = static_cast<int>((opt->zProf0-opt->min)/opt->dz);
1191 else if (imin >= bins)
1195 diff = profile[imin];
1199 for (i = 0; i < bins; i++)
1205 //! Make an array of random integers (used for bootstrapping)
1206 static void getRandomIntArray(int nPull, int blockLength, int* randomArray, gmx::DefaultRandomEngine * rng)
1208 gmx::UniformIntDistribution<int> dist(0, blockLength-1);
1210 int ipull, blockBase, nr, ipullRandom;
1212 if (blockLength == 0)
1214 blockLength = nPull;
1217 for (ipull = 0; ipull < nPull; ipull++)
1219 blockBase = (ipull/blockLength)*blockLength;
1221 { /* make sure nothing bad happens in the last block */
1222 nr = dist(*rng); // [0,blockLength-1]
1223 ipullRandom = blockBase + nr;
1225 while (ipullRandom >= nPull);
1226 if (ipullRandom < 0 || ipullRandom >= nPull)
1228 gmx_fatal(FARGS, "Ups, random iWin = %d, nPull = %d, nr = %d, "
1229 "blockLength = %d, blockBase = %d\n",
1230 ipullRandom, nPull, nr, blockLength, blockBase);
1232 randomArray[ipull] = ipullRandom;
1234 /*for (ipull=0; ipull<nPull; ipull++)
1235 printf("%d ",randomArray[ipull]); printf("\n"); */
1238 /*! \brief Set pull group information of a synthetic histogram
1240 * This is used when bootstapping new trajectories and thereby create new histogtrams,
1241 * but it is not required if we bootstrap complete histograms.
1243 static void copy_pullgrp_to_synthwindow(t_UmbrellaWindow *synthWindow,
1244 t_UmbrellaWindow *thisWindow, int pullid)
1246 synthWindow->N [0] = thisWindow->N [pullid];
1247 synthWindow->Histo [0] = thisWindow->Histo [pullid];
1248 synthWindow->pos [0] = thisWindow->pos [pullid];
1249 synthWindow->z [0] = thisWindow->z [pullid];
1250 synthWindow->k [0] = thisWindow->k [pullid];
1251 synthWindow->bContrib[0] = thisWindow->bContrib [pullid];
1252 synthWindow->g [0] = thisWindow->g [pullid];
1253 synthWindow->bsWeight[0] = thisWindow->bsWeight [pullid];
1256 /*! \brief Calculate cumulative distribution function of of all histograms.
1258 * This allow to create random number sequences
1259 * which are distributed according to the histograms. Required to generate
1260 * the "synthetic" histograms for the Bootstrap method
1262 static void calc_cumulatives(t_UmbrellaWindow *window, int nWindows,
1263 t_UmbrellaOptions *opt, const char *fnhist, const char *xlabel)
1267 char *fn = nullptr, *buf = nullptr;
1270 if (opt->bs_verbose)
1272 snew(fn, std::strlen(fnhist)+10);
1273 snew(buf, std::strlen(fnhist)+10);
1274 sprintf(fn, "%s_cumul.xvg", std::strncpy(buf, fnhist, std::strlen(fnhist)-4));
1275 fp = xvgropen(fn, "CDFs of umbrella windows", xlabel, "CDF", opt->oenv);
1279 for (i = 0; i < nWindows; i++)
1281 snew(window[i].cum, window[i].nPull);
1282 for (j = 0; j < window[i].nPull; j++)
1284 snew(window[i].cum[j], nbin+1);
1285 window[i].cum[j][0] = 0.;
1286 for (k = 1; k <= nbin; k++)
1288 window[i].cum[j][k] = window[i].cum[j][k-1]+window[i].Histo[j][k-1];
1291 /* normalize CDFs. Ensure cum[nbin]==1 */
1292 last = window[i].cum[j][nbin];
1293 for (k = 0; k <= nbin; k++)
1295 window[i].cum[j][k] /= last;
1300 printf("Cumulative distribution functions of all histograms created.\n");
1301 if (opt->bs_verbose)
1303 for (k = 0; k <= nbin; k++)
1305 fprintf(fp, "%g\t", opt->min+k*opt->dz);
1306 for (i = 0; i < nWindows; i++)
1308 for (j = 0; j < window[i].nPull; j++)
1310 fprintf(fp, "%g\t", window[i].cum[j][k]);
1315 printf("Wrote cumulative distribution functions to %s\n", fn);
1323 /*! \brief Return j such that xx[j] <= x < xx[j+1]
1325 * This is used to generate a random sequence distributed according to a histogram
1327 static void searchCumulative(const double xx[], int n, double x, int *j)
1349 else if (x == xx[n-1])
1359 //! Bootstrap new trajectories and thereby generate new (bootstrapped) histograms
1360 static void create_synthetic_histo(t_UmbrellaWindow *synthWindow, t_UmbrellaWindow *thisWindow,
1361 int pullid, t_UmbrellaOptions *opt)
1363 int N, i, nbins, r_index, ibin;
1364 double r, tausteps = 0.0, a, ap, dt, x, invsqrt2, g, y, sig = 0., z, mu = 0.;
1367 N = thisWindow->N[pullid];
1368 dt = thisWindow->dt;
1369 nbins = thisWindow->nBin;
1371 /* tau = autocorrelation time */
1372 if (opt->tauBootStrap > 0.0)
1374 tausteps = opt->tauBootStrap/dt;
1376 else if (opt->bTauIntGiven || opt->bCalcTauInt)
1378 /* calc tausteps from g=1+2tausteps */
1379 g = thisWindow->g[pullid];
1385 "When generating hypothetical trajectories from given umbrella histograms,\n"
1386 "autocorrelation times (ACTs) are required. Otherwise the statistical error\n"
1387 "cannot be predicted. You have 3 options:\n"
1388 "1) Make gmx wham estimate the ACTs (options -ac and -acsig).\n"
1389 "2) Calculate the ACTs by yourself (e.g. with g_analyze) and provide them\n");
1391 " with option -iiact for all umbrella windows.\n"
1392 "3) If all ACTs are identical and know, you can define them with -bs-tau.\n"
1393 " Use option (3) only if you are sure what you're doing, you may severely\n"
1394 " underestimate the error if a too small ACT is given.\n");
1395 gmx_fatal(FARGS, "%s", errstr);
1398 synthWindow->N [0] = N;
1399 synthWindow->pos [0] = thisWindow->pos[pullid];
1400 synthWindow->z [0] = thisWindow->z[pullid];
1401 synthWindow->k [0] = thisWindow->k[pullid];
1402 synthWindow->bContrib[0] = thisWindow->bContrib[pullid];
1403 synthWindow->g [0] = thisWindow->g [pullid];
1404 synthWindow->bsWeight[0] = thisWindow->bsWeight[pullid];
1406 for (i = 0; i < nbins; i++)
1408 synthWindow->Histo[0][i] = 0.;
1411 if (opt->bsMethod == bsMethod_trajGauss)
1413 sig = thisWindow->sigma [pullid];
1414 mu = thisWindow->aver [pullid];
1417 /* Genrate autocorrelated Gaussian random variable with autocorrelation time tau
1419 If x and y are random numbers from N(0,1) (Gaussian with average 0 and sigma=1),
1421 z = a*x + sqrt(1-a^2)*y
1422 is also from N(0,1), and cov(z,x) = a. Thus, by gerenating a sequence
1423 x' = a*x + sqrt(1-a^2)*y, the sequnce x(t) is from N(0,1) and has an autocorrelation
1425 C(t) = exp(-t/tau) with tau=-1/ln(a)
1427 Then, use error function to turn the Gaussian random variable into a uniformly
1428 distributed one in [0,1]. Eventually, use cumulative distribution function of
1429 histogram to get random variables distributed according to histogram.
1430 Note: The ACT of the flat distribution and of the generated histogram is not
1431 100% exactly tau, but near tau (my test was 3.8 instead of 4).
1433 a = std::exp(-1.0/tausteps);
1434 ap = std::sqrt(1.0-a*a);
1435 invsqrt2 = 1.0/std::sqrt(2.0);
1437 /* init random sequence */
1438 x = opt->normalDistribution(opt->rng);
1440 if (opt->bsMethod == bsMethod_traj)
1442 /* bootstrap points from the umbrella histograms */
1443 for (i = 0; i < N; i++)
1445 y = opt->normalDistribution(opt->rng);
1447 /* get flat distribution in [0,1] using cumulative distribution function of Gauusian
1448 Note: CDF(Gaussian) = 0.5*{1+erf[x/sqrt(2)]}
1450 r = 0.5*(1+std::erf(x*invsqrt2));
1451 searchCumulative(thisWindow->cum[pullid], nbins+1, r, &r_index);
1452 synthWindow->Histo[0][r_index] += 1.;
1455 else if (opt->bsMethod == bsMethod_trajGauss)
1457 /* bootstrap points from a Gaussian with the same average and sigma
1458 as the respective umbrella histogram. The idea was, that -given
1459 limited sampling- the bootstrapped histograms are otherwise biased
1460 from the limited sampling of the US histos. However, bootstrapping from
1461 the Gaussian seems to yield a similar estimate. */
1465 y = opt->normalDistribution(opt->rng);
1468 ibin = static_cast<int> (std::floor((z-opt->min)/opt->dz));
1473 while ( (ibin += nbins) < 0)
1478 else if (ibin >= nbins)
1480 while ( (ibin -= nbins) >= nbins)
1487 if (ibin >= 0 && ibin < nbins)
1489 synthWindow->Histo[0][ibin] += 1.;
1496 gmx_fatal(FARGS, "Unknown bsMethod (id %d). That should not happen.\n", opt->bsMethod);
1500 /*! \brief Write all histograms to a file
1502 * If bs_index>=0, a number is added to the output file name to allow the ouput of all
1503 * sets of bootstrapped histograms.
1505 static void print_histograms(const char *fnhist, t_UmbrellaWindow * window, int nWindows,
1506 int bs_index, t_UmbrellaOptions *opt, const char *xlabel)
1508 char *fn = nullptr, *buf = nullptr, title[256];
1514 snew(fn, std::strlen(fnhist)+10);
1515 snew(buf, std::strlen(fnhist)+1);
1516 sprintf(fn, "%s_bs%d.xvg", std::strncpy(buf, fnhist, std::strlen(fnhist)-4), bs_index);
1517 sprintf(title, "Umbrella histograms. Bootstrap #%d", bs_index);
1521 fn = gmx_strdup(fnhist);
1522 std::strcpy(title, "Umbrella histograms");
1525 fp = xvgropen(fn, title, xlabel, "count", opt->oenv);
1528 /* Write histograms */
1529 for (l = 0; l < bins; ++l)
1531 fprintf(fp, "%e\t", (l+0.5)*opt->dz+opt->min);
1532 for (i = 0; i < nWindows; ++i)
1534 for (j = 0; j < window[i].nPull; ++j)
1536 fprintf(fp, "%e\t", window[i].Histo[j][l]);
1543 printf("Wrote %s\n", fn);
1551 //! Make random weights for histograms for the Bayesian bootstrap of complete histograms)
1552 static void setRandomBsWeights(t_UmbrellaWindow *synthwin, int nAllPull, t_UmbrellaOptions *opt)
1556 gmx::UniformRealDistribution<real> dist(0, nAllPull);
1560 /* generate ordered random numbers between 0 and nAllPull */
1561 for (i = 0; i < nAllPull-1; i++)
1563 r[i] = dist(opt->rng);
1565 std::sort(r, r+nAllPull-1);
1566 r[nAllPull-1] = 1.0*nAllPull;
1568 synthwin[0].bsWeight[0] = r[0];
1569 for (i = 1; i < nAllPull; i++)
1571 synthwin[i].bsWeight[0] = r[i]-r[i-1];
1574 /* avoid to have zero weight by adding a tiny value */
1575 for (i = 0; i < nAllPull; i++)
1577 if (synthwin[i].bsWeight[0] < 1e-5)
1579 synthwin[i].bsWeight[0] = 1e-5;
1586 //! The main bootstrapping routine
1587 static void do_bootstrapping(const char *fnres, const char* fnprof, const char *fnhist,
1588 const char *xlabel, char* ylabel, double *profile,
1589 t_UmbrellaWindow * window, int nWindows, t_UmbrellaOptions *opt)
1591 t_UmbrellaWindow * synthWindow;
1592 double *bsProfile, *bsProfiles_av, *bsProfiles_av2, maxchange = 1e20, tmp, stddev;
1593 int i, j, *randomArray = nullptr, winid, pullid, ib;
1594 int iAllPull, nAllPull, *allPull_winId, *allPull_pullId;
1596 gmx_bool bExact = FALSE;
1598 /* init random generator */
1599 if (opt->bsSeed == 0)
1601 opt->bsSeed = static_cast<int>(gmx::makeRandomSeed());
1603 opt->rng.seed(opt->bsSeed);
1605 snew(bsProfile, opt->bins);
1606 snew(bsProfiles_av, opt->bins);
1607 snew(bsProfiles_av2, opt->bins);
1609 /* Create array of all pull groups. Note that different windows
1610 may have different nr of pull groups
1611 First: Get total nr of pull groups */
1613 for (i = 0; i < nWindows; i++)
1615 nAllPull += window[i].nPull;
1617 snew(allPull_winId, nAllPull);
1618 snew(allPull_pullId, nAllPull);
1620 /* Setup one array of all pull groups */
1621 for (i = 0; i < nWindows; i++)
1623 for (j = 0; j < window[i].nPull; j++)
1625 allPull_winId[iAllPull] = i;
1626 allPull_pullId[iAllPull] = j;
1631 /* setup stuff for synthetic windows */
1632 snew(synthWindow, nAllPull);
1633 for (i = 0; i < nAllPull; i++)
1635 synthWindow[i].nPull = 1;
1636 synthWindow[i].nBin = opt->bins;
1637 snew(synthWindow[i].Histo, 1);
1638 if (opt->bsMethod == bsMethod_traj || opt->bsMethod == bsMethod_trajGauss)
1640 snew(synthWindow[i].Histo[0], opt->bins);
1642 snew(synthWindow[i].N, 1);
1643 snew(synthWindow[i].pos, 1);
1644 snew(synthWindow[i].z, 1);
1645 snew(synthWindow[i].k, 1);
1646 snew(synthWindow[i].bContrib, 1);
1647 snew(synthWindow[i].g, 1);
1648 snew(synthWindow[i].bsWeight, 1);
1651 switch (opt->bsMethod)
1654 snew(randomArray, nAllPull);
1655 printf("\n\nWhen computing statistical errors by bootstrapping entire histograms:\n");
1656 please_cite(stdout, "Hub2006");
1658 case bsMethod_BayesianHist:
1659 /* just copy all histogams into synthWindow array */
1660 for (i = 0; i < nAllPull; i++)
1662 winid = allPull_winId [i];
1663 pullid = allPull_pullId[i];
1664 copy_pullgrp_to_synthwindow(synthWindow+i, window+winid, pullid);
1668 case bsMethod_trajGauss:
1669 calc_cumulatives(window, nWindows, opt, fnhist, xlabel);
1672 gmx_fatal(FARGS, "Unknown bootstrap method. That should not have happened.\n");
1675 /* do bootstrapping */
1676 fp = xvgropen(fnprof, "Bootstrap profiles", xlabel, ylabel, opt->oenv);
1677 for (ib = 0; ib < opt->nBootStrap; ib++)
1679 printf(" *******************************************\n"
1680 " ******** Start bootstrap nr %d ************\n"
1681 " *******************************************\n", ib+1);
1683 switch (opt->bsMethod)
1686 /* bootstrap complete histograms from given histograms */
1687 getRandomIntArray(nAllPull, opt->histBootStrapBlockLength, randomArray, &opt->rng);
1688 for (i = 0; i < nAllPull; i++)
1690 winid = allPull_winId [randomArray[i]];
1691 pullid = allPull_pullId[randomArray[i]];
1692 copy_pullgrp_to_synthwindow(synthWindow+i, window+winid, pullid);
1695 case bsMethod_BayesianHist:
1696 /* keep histos, but assign random weights ("Bayesian bootstrap") */
1697 setRandomBsWeights(synthWindow, nAllPull, opt);
1700 case bsMethod_trajGauss:
1701 /* create new histos from given histos, that is generate new hypothetical
1703 for (i = 0; i < nAllPull; i++)
1705 winid = allPull_winId[i];
1706 pullid = allPull_pullId[i];
1707 create_synthetic_histo(synthWindow+i, window+winid, pullid, opt);
1712 /* write histos in case of verbose output */
1713 if (opt->bs_verbose)
1715 print_histograms(fnhist, synthWindow, nAllPull, ib, opt, xlabel);
1722 std::memcpy(bsProfile, profile, opt->bins*sizeof(double)); /* use profile as guess */
1725 if ( (i%opt->stepUpdateContrib) == 0)
1727 setup_acc_wham(bsProfile, synthWindow, nAllPull, opt);
1729 if (maxchange < opt->Tolerance)
1733 if (((i%opt->stepchange) == 0 || i == 1) && i != 0)
1735 printf("\t%4d) Maximum change %e\n", i, maxchange);
1737 calc_profile(bsProfile, synthWindow, nAllPull, opt, bExact);
1740 while ( (maxchange = calc_z(bsProfile, synthWindow, nAllPull, opt, bExact)) > opt->Tolerance || !bExact);
1741 printf("\tConverged in %d iterations. Final maximum change %g\n", i, maxchange);
1745 prof_normalization_and_unit(bsProfile, opt);
1748 /* symmetrize profile around z=0 */
1751 symmetrizeProfile(bsProfile, opt);
1754 /* save stuff to get average and stddev */
1755 for (i = 0; i < opt->bins; i++)
1758 bsProfiles_av[i] += tmp;
1759 bsProfiles_av2[i] += tmp*tmp;
1760 fprintf(fp, "%e\t%e\n", (i+0.5)*opt->dz+opt->min, tmp);
1762 fprintf(fp, "%s\n", output_env_get_print_xvgr_codes(opt->oenv) ? "&" : "");
1766 /* write average and stddev */
1767 fp = xvgropen(fnres, "Average and stddev from bootstrapping", xlabel, ylabel, opt->oenv);
1768 if (output_env_get_print_xvgr_codes(opt->oenv))
1770 fprintf(fp, "@TYPE xydy\n");
1772 for (i = 0; i < opt->bins; i++)
1774 bsProfiles_av [i] /= opt->nBootStrap;
1775 bsProfiles_av2[i] /= opt->nBootStrap;
1776 tmp = bsProfiles_av2[i]-gmx::square(bsProfiles_av[i]);
1777 stddev = (tmp >= 0.) ? std::sqrt(tmp) : 0.; /* Catch rouding errors */
1778 fprintf(fp, "%e\t%e\t%e\n", (i+0.5)*opt->dz+opt->min, bsProfiles_av [i], stddev);
1781 printf("Wrote boot strap result to %s\n", fnres);
1784 //! Return type of input file based on file extension (xvg, pdo, or tpr)
1785 static int whaminFileType(char *fn)
1788 len = std::strlen(fn);
1789 if (std::strcmp(fn+len-3, "tpr") == 0)
1793 else if (std::strcmp(fn+len-3, "xvg") == 0 || std::strcmp(fn+len-6, "xvg.gz") == 0)
1795 return whamin_pullxf;
1797 else if (std::strcmp(fn+len-3, "pdo") == 0 || std::strcmp(fn+len-6, "pdo.gz") == 0)
1803 gmx_fatal(FARGS, "Unknown file type of %s. Should be tpr, xvg, or pdo.\n", fn);
1807 //! Read the files names in pdo-files.dat, pullf/x-files.dat, tpr-files.dat
1808 static void read_wham_in(const char *fn, char ***filenamesRet, int *nfilesRet,
1809 t_UmbrellaOptions *opt)
1811 char **filename = nullptr, tmp[WHAM_MAXFILELEN+2];
1812 int nread, sizenow, i, block = 1;
1815 fp = gmx_ffopen(fn, "r");
1818 while (fgets(tmp, sizeof(tmp), fp) != nullptr)
1820 if (std::strlen(tmp) >= WHAM_MAXFILELEN)
1822 gmx_fatal(FARGS, "Filename too long in %s. Only %d characters allowed.\n", fn, WHAM_MAXFILELEN);
1824 if (nread >= sizenow)
1827 srenew(filename, sizenow);
1828 for (i = sizenow-block; i < sizenow; i++)
1830 snew(filename[i], WHAM_MAXFILELEN);
1833 /* remove newline if there is one */
1834 if (tmp[std::strlen(tmp)-1] == '\n')
1836 tmp[std::strlen(tmp)-1] = '\0';
1838 std::strcpy(filename[nread], tmp);
1841 printf("Found file %s in %s\n", filename[nread], fn);
1845 *filenamesRet = filename;
1849 //! Open a file or a pipe to a gzipped file
1850 static FILE *open_pdo_pipe(const char *fn, t_UmbrellaOptions *opt, gmx_bool *bPipeOpen)
1852 char Buffer[1024], gunzip[1024], *Path = nullptr;
1853 FILE *pipe = nullptr;
1854 static gmx_bool bFirst = true;
1856 /* gzipped pdo file? */
1857 if ((std::strcmp(fn+std::strlen(fn)-3, ".gz") == 0))
1859 /* search gunzip executable */
1860 if (!(Path = getenv("GMX_PATH_GZIP")))
1862 if (gmx_fexist("/bin/gunzip"))
1864 sprintf(gunzip, "%s", "/bin/gunzip");
1866 else if (gmx_fexist("/usr/bin/gunzip"))
1868 sprintf(gunzip, "%s", "/usr/bin/gunzip");
1872 gmx_fatal(FARGS, "Cannot find executable gunzip in /bin or /usr/bin.\n"
1873 "You may want to define the path to gunzip "
1874 "with the environment variable GMX_PATH_GZIP.", gunzip);
1879 sprintf(gunzip, "%s/gunzip", Path);
1880 if (!gmx_fexist(gunzip))
1882 gmx_fatal(FARGS, "Cannot find executable %s. Please define the path to gunzip"
1883 " in the environmental varialbe GMX_PATH_GZIP.", gunzip);
1888 printf("Using gunzip executable %s\n", gunzip);
1891 if (!gmx_fexist(fn))
1893 gmx_fatal(FARGS, "File %s does not exist.\n", fn);
1895 sprintf(Buffer, "%s -c < %s", gunzip, fn);
1898 printf("Executing command '%s'\n", Buffer);
1901 if ((pipe = popen(Buffer, "r")) == nullptr)
1903 gmx_fatal(FARGS, "Unable to open pipe to `%s'\n", Buffer);
1906 gmx_fatal(FARGS, "Cannot open a compressed file on platform without pipe support");
1912 pipe = gmx_ffopen(fn, "r");
1919 //! Close file or pipe
1920 static void pdo_close_file(FILE *fp)
1929 //! Reading all pdo files
1930 static void read_pdo_files(char **fn, int nfiles, t_UmbrellaHeader* header,
1931 t_UmbrellaWindow *window, t_UmbrellaOptions *opt)
1934 real mintmp, maxtmp, done = 0.;
1937 /* char Buffer0[1000]; */
1941 gmx_fatal(FARGS, "No files found. Hick.");
1944 /* if min and max are not given, get min and max from the input files */
1947 printf("Automatic determination of boundaries from %d pdo files...\n", nfiles);
1950 for (i = 0; i < nfiles; ++i)
1952 file = open_pdo_pipe(fn[i], opt, &bPipeOpen);
1953 /*fgets(Buffer0,999,file);
1954 fprintf(stderr,"First line '%s'\n",Buffer0); */
1955 done = 100.0*(i+1)/nfiles;
1956 fprintf(stdout, "\rOpening %s ... [%2.0f%%]", fn[i], done); fflush(stdout);
1961 read_pdo_header(file, header, opt);
1962 /* here only determine min and max of this window */
1963 read_pdo_data(file, header, i, nullptr, opt, TRUE, &mintmp, &maxtmp);
1964 if (maxtmp > opt->max)
1968 if (mintmp < opt->min)
1974 pdo_close_file(file);
1982 printf("\nDetermined boundaries to %f and %f\n\n", opt->min, opt->max);
1983 if (opt->bBoundsOnly)
1985 printf("Found option -boundsonly, now exiting.\n");
1989 /* store stepsize in profile */
1990 opt->dz = (opt->max-opt->min)/opt->bins;
1992 /* Having min and max, we read in all files */
1993 /* Loop over all files */
1994 for (i = 0; i < nfiles; ++i)
1996 done = 100.0*(i+1)/nfiles;
1997 fprintf(stdout, "\rOpening %s ... [%2.0f%%]", fn[i], done); fflush(stdout);
2002 file = open_pdo_pipe(fn[i], opt, &bPipeOpen);
2003 read_pdo_header(file, header, opt);
2004 /* load data into window */
2005 read_pdo_data(file, header, i, window, opt, FALSE, nullptr, nullptr);
2006 if ((window+i)->Ntot[0] == 0)
2008 fprintf(stderr, "\nWARNING, no data points read from file %s (check -b option)\n", fn[i]);
2012 pdo_close_file(file);
2020 for (i = 0; i < nfiles; ++i)
2027 //! translate 0/1 to N/Y to write pull dimensions
2028 #define int2YN(a) (((a) == 0) ? ("N") : ("Y"))
2030 //! Read pull groups from a tpr file (including position, force const, geometry, number of groups)
2031 static void read_tpr_header(const char *fn, t_UmbrellaHeader* header, t_UmbrellaOptions *opt, t_coordselection *coordsel)
2033 t_inputrec irInstance;
2034 t_inputrec *ir = &irInstance;
2036 static int first = 1;
2038 /* printf("Reading %s \n",fn); */
2039 read_tpx_state(fn, ir, &state, nullptr);
2043 gmx_fatal(FARGS, "This is not a tpr with COM pulling");
2045 if (ir->pull->ncoord == 0)
2047 gmx_fatal(FARGS, "No pull coordinates found in %s", fn);
2050 /* Read overall pull info */
2051 header->npullcrds = ir->pull->ncoord;
2052 header->bPrintCOM = ir->pull->bPrintCOM;
2053 header->bPrintRefValue = ir->pull->bPrintRefValue;
2054 header->bPrintComp = ir->pull->bPrintComp;
2056 /* Read pull coordinates */
2057 snew(header->pcrd, header->npullcrds);
2058 for (int i = 0; i < ir->pull->ncoord; i++)
2060 header->pcrd[i].pull_type = ir->pull->coord[i].eType;
2061 header->pcrd[i].geometry = ir->pull->coord[i].eGeom;
2062 header->pcrd[i].ngroup = ir->pull->coord[i].ngroup;
2063 header->pcrd[i].k = ir->pull->coord[i].k;
2064 header->pcrd[i].init_dist = ir->pull->coord[i].init;
2066 copy_ivec(ir->pull->coord[i].dim, header->pcrd[i].dim);
2067 header->pcrd[i].ndim = header->pcrd[i].dim[XX] + header->pcrd[i].dim[YY] + header->pcrd[i].dim[ZZ];
2069 std::strcpy(header->pcrd[i].coord_unit,
2070 pull_coordinate_units(&ir->pull->coord[i]));
2072 if (ir->efep != efepNO && ir->pull->coord[i].k != ir->pull->coord[i].kB)
2074 gmx_fatal(FARGS, "Seems like you did free-energy perturbation, and you perturbed the force constant."
2075 " This is not supported.\n");
2077 if (coordsel && (coordsel->n != ir->pull->ncoord))
2079 gmx_fatal(FARGS, "Found %d pull coordinates in %s, but %d columns in the respective line\n"
2080 "coordinate selection file (option -is)\n", ir->pull->ncoord, fn, coordsel->n);
2084 /* Check pull coords for consistency */
2086 ivec thedim = { 0, 0, 0 };
2087 bool geometryIsSet = false;
2088 for (int i = 0; i < ir->pull->ncoord; i++)
2090 if (coordsel == nullptr || coordsel->bUse[i])
2092 if (header->pcrd[i].pull_type != epullUMBRELLA)
2094 gmx_fatal(FARGS, "%s: Pull coordinate %d is of type \"%s\", expected \"umbrella\". Only umbrella coodinates can enter WHAM.\n"
2095 "If you have umrella and non-umbrella coordinates, you can select the umbrella coordinates with gmx wham -is\n",
2096 fn, i+1, epull_names[header->pcrd[i].pull_type]);
2100 geom = header->pcrd[i].geometry;
2101 copy_ivec(header->pcrd[i].dim, thedim);
2102 geometryIsSet = true;
2104 if (geom != header->pcrd[i].geometry)
2106 gmx_fatal(FARGS, "%s: Your pull coordinates have different pull geometry (coordinate 1: %s, coordinate %d: %s)\n"
2107 "If you want to use only some pull coordinates in WHAM, please select them with option gmx wham -is\n",
2108 fn, epullg_names[geom], i+1, epullg_names[header->pcrd[i].geometry]);
2110 if (thedim[XX] != header->pcrd[i].dim[XX] || thedim[YY] != header->pcrd[i].dim[YY] || thedim[ZZ] != header->pcrd[i].dim[ZZ])
2112 gmx_fatal(FARGS, "%s: Your pull coordinates have different pull dimensions (coordinate 1: %s %s %s, coordinate %d: %s %s %s)\n"
2113 "If you want to use only some pull coordinates in WHAM, please select them with option gmx wham -is\n",
2114 fn, int2YN(thedim[XX]), int2YN(thedim[YY]), int2YN(thedim[ZZ]), i+1,
2115 int2YN(header->pcrd[i].dim[XX]), int2YN(header->pcrd[i].dim[YY]), int2YN(header->pcrd[i].dim[ZZ]));
2117 if (header->pcrd[i].geometry == epullgCYL)
2119 if (header->pcrd[i].dim[XX] || header->pcrd[i].dim[YY] || (!header->pcrd[i].dim[ZZ]))
2121 gmx_fatal(FARGS, "With pull geometry 'cylinder', expected pulling in Z direction only.\n"
2122 "However, found dimensions [%s %s %s]\n",
2123 int2YN(header->pcrd[i].dim[XX]), int2YN(header->pcrd[i].dim[YY]),
2124 int2YN(header->pcrd[i].dim[ZZ]));
2127 if (header->pcrd[i].k <= 0.0)
2129 gmx_fatal(FARGS, "%s: Pull coordinate %d has force constant of of %g in %s.\n"
2130 "That doesn't seem to be an Umbrella tpr.\n",
2131 fn, i+1, header->pcrd[i].k);
2136 if (opt->verbose || first)
2138 printf("\nFile %s, %d coordinates, with these options:\n", fn, header->npullcrds);
2140 for (int i = 0; i < ir->pull->ncoord; i++)
2142 int lentmp = strlen(epullg_names[header->pcrd[i].geometry]);
2143 maxlen = (lentmp > maxlen) ? lentmp : maxlen;
2146 sprintf(fmt, "\tGeometry %%-%ds k = %%-8g position = %%-8g dimensions [%%s %%s %%s] (%%d dimensions). Used: %%s\n",
2148 for (int i = 0; i < ir->pull->ncoord; i++)
2150 bool use = (coordsel == nullptr || coordsel->bUse[i]);
2152 epullg_names[header->pcrd[i].geometry], header->pcrd[i].k, header->pcrd[i].init_dist,
2153 int2YN(header->pcrd[i].dim[XX]), int2YN(header->pcrd[i].dim[YY]), int2YN(header->pcrd[i].dim[ZZ]),
2154 header->pcrd[i].ndim, use ? "Yes" : "No");
2155 printf("\tPull group coordinates of %d groups expected in pullx files.\n", ir->pull->bPrintCOM ? header->pcrd[i].ngroup : 0);
2157 printf("\tReference value of the coordinate%s expected in pullx files.\n",
2158 header->bPrintRefValue ? "" : " not");
2160 if (!opt->verbose && first)
2162 printf("\tUse option -v to see this output for all input tpr files\n\n");
2168 //! Read pullx.xvg or pullf.xvg
2169 static void read_pull_xf(const char *fn, t_UmbrellaHeader * header,
2170 t_UmbrellaWindow * window,
2171 t_UmbrellaOptions *opt,
2172 gmx_bool bGetMinMax, real *mintmp, real *maxtmp,
2173 t_coordselection *coordsel)
2175 double **y = nullptr, pos = 0., t, force, time0 = 0., dt;
2176 int ny, nt, bins, ibin, i, g, gUsed, dstep = 1;
2177 int nColExpect, ntot, column;
2178 real min, max, minfound = 1e20, maxfound = -1e20;
2179 gmx_bool dt_ok, timeok;
2180 const char *quantity;
2181 const int blocklen = 4096;
2182 int *lennow = nullptr;
2183 static gmx_bool bFirst = TRUE;
2186 * Data columns in pull output:
2187 * - in force output pullf.xvg:
2188 * No reference columns, one column per pull coordinate
2190 * - in position output pullx.xvg:
2191 * * optionally, ndim columns for COMs of all groups (depending on on mdp options pull-print-com);
2192 * * The displacement, always one column. Note: with pull-print-components = yes, the dx/dy/dz would
2193 * be written separately into pullx file, but this is not supported and throws an error below;
2194 * * optionally, the position of the reference coordinate (depending on pull-print-ref-value)
2197 if (header->bPrintComp && opt->bPullx)
2199 gmx_fatal(FARGS, "gmx wham cannot read pullx files if the components of the coordinate was written\n"
2200 "(mdp option pull-print-components). Provide the pull force files instead (with option -if).\n");
2203 int *nColThisCrd, *nColCOMCrd, *nColRefCrd;
2204 snew(nColThisCrd, header->npullcrds);
2205 snew(nColCOMCrd, header->npullcrds);
2206 snew(nColRefCrd, header->npullcrds);
2210 /* pullf reading: simply one column per coordinate */
2211 for (g = 0; g < header->npullcrds; g++)
2220 /* pullx reading. Note explanation above. */
2221 for (g = 0; g < header->npullcrds; g++)
2223 nColRefCrd[g] = (header->bPrintRefValue ? 1 : 0);
2224 nColCOMCrd[g] = (header->bPrintCOM ? header->pcrd[g].ndim*header->pcrd[g].ngroup : 0);
2225 nColThisCrd[g] = 1 + nColCOMCrd[g] + nColRefCrd[g];
2229 nColExpect = 1; /* time column */
2230 for (g = 0; g < header->npullcrds; g++)
2232 nColExpect += nColThisCrd[g];
2235 /* read pullf or pullx. Could be optimized if min and max are given. */
2236 nt = read_xvg(fn, &y, &ny);
2238 /* Check consistency */
2239 quantity = opt->bPullx ? "position" : "force";
2242 gmx_fatal(FARGS, "Empty pull %s file %s\n", quantity, fn);
2244 if (bFirst || opt->verbose)
2246 printf("\nReading pull %s file %s, expecting %d columns:\n", quantity, fn, nColExpect);
2247 for (i = 0; i < header->npullcrds; i++)
2249 printf("\tColumns for pull coordinate %d\n", i+1);
2250 printf("\t\treaction coordinate: %d\n"
2251 "\t\tcenter-of-mass of groups: %d\n"
2252 "\t\treference position column: %s\n",
2253 1, nColCOMCrd[i], (header->bPrintRefValue ? "Yes" : "No"));
2255 printf("\tFound %d times in %s\n", nt, fn);
2258 if (nColExpect != ny)
2260 gmx_fatal(FARGS, "Expected %d columns (including time column) in %s, but found %d."
2261 " Maybe you confused options -if and -ix ?", nColExpect, fn, ny);
2272 window->dt = y[0][1]-y[0][0];
2274 else if (opt->nBootStrap && opt->tauBootStrap != 0.0)
2276 fprintf(stderr, "\n *** WARNING, Could not determine time step in %s\n", fn);
2279 /* Need to alocate memory and set up structure for windows */
2282 /* Use only groups selected with option -is file */
2283 if (header->npullcrds != coordsel->n)
2285 gmx_fatal(FARGS, "tpr file contains %d pull groups, but expected %d from group selection file\n",
2286 header->npullcrds, coordsel->n);
2288 window->nPull = coordsel->nUse;
2292 window->nPull = header->npullcrds;
2295 window->nBin = bins;
2296 snew(window->Histo, window->nPull);
2297 snew(window->z, window->nPull);
2298 snew(window->k, window->nPull);
2299 snew(window->pos, window->nPull);
2300 snew(window->N, window->nPull);
2301 snew(window->Ntot, window->nPull);
2302 snew(window->g, window->nPull);
2303 snew(window->bsWeight, window->nPull);
2304 window->bContrib = nullptr;
2306 if (opt->bCalcTauInt)
2308 snew(window->ztime, window->nPull);
2312 window->ztime = nullptr;
2314 snew(lennow, window->nPull);
2316 for (g = 0; g < window->nPull; ++g)
2319 window->bsWeight [g] = 1.;
2321 window->Ntot [g] = 0;
2323 snew(window->Histo[g], bins);
2325 if (opt->bCalcTauInt)
2327 window->ztime[g] = nullptr;
2331 /* Copying umbrella center and force const is more involved since not
2332 all pull groups from header (tpr file) may be used in window variable */
2333 for (g = 0, gUsed = 0; g < header->npullcrds; ++g)
2335 if (coordsel && !coordsel->bUse[g])
2339 window->k [gUsed] = header->pcrd[g].k;
2340 window->pos[gUsed] = header->pcrd[g].init_dist;
2345 { /* only determine min and max */
2348 min = max = bins = 0; /* Get rid of warnings */
2352 for (i = 0; i < nt; i++)
2354 /* Do you want that time frame? */
2355 t = 1.0/1000*( gmx::roundToInt64((y[0][i]*1000))); /* round time to fs */
2357 /* get time step of pdo file and get dstep from opt->dt */
2367 dstep = gmx::roundToInt(opt->dt/dt);
2375 window->dt = dt*dstep;
2379 dt_ok = (i%dstep == 0);
2380 timeok = (dt_ok && t >= opt->tmin && t <= opt->tmax);
2382 printf(" time = %f, (tmin,tmax)=(%e,%e), dt_ok=%d timeok=%d\n",
2383 t,opt->tmin, opt->tmax, dt_ok,timeok); */
2386 /* Note: if coordsel == NULL:
2387 * all groups in pullf/x file are stored in this window, and gUsed == g
2388 * if coordsel != NULL:
2389 * only groups with coordsel.bUse[g]==TRUE are stored. gUsed is not always equal g
2392 for (g = 0; g < header->npullcrds; ++g)
2394 /* was this group selected for application in WHAM? */
2395 if (coordsel && !coordsel->bUse[g])
2403 /* y has 1 time column y[0] and one column per force y[1],...,y[nCrds] */
2405 pos = -force/header->pcrd[g].k + header->pcrd[g].init_dist;
2409 /* Pick the correct column index.
2410 Note that there is always exactly one displacement column.
2413 for (int j = 0; j < g; j++)
2415 column += nColThisCrd[j];
2420 /* printf("crd %d dpos %f poseq %f pos %f \n",g,dpos,poseq,pos); */
2434 if (gUsed >= window->nPull)
2436 gmx_fatal(FARGS, "gUsed too large (%d, nPull=%d). This error should have been caught before.\n",
2437 gUsed, window->nPull);
2440 if (opt->bCalcTauInt && !bGetMinMax)
2442 /* save time series for autocorrelation analysis */
2443 ntot = window->Ntot[gUsed];
2444 /* printf("i %d, ntot %d, lennow[g] = %d\n",i,ntot,lennow[g]); */
2445 if (ntot >= lennow[gUsed])
2447 lennow[gUsed] += blocklen;
2448 srenew(window->ztime[gUsed], lennow[gUsed]);
2450 window->ztime[gUsed][ntot] = pos;
2453 ibin = static_cast<int> (std::floor((pos-min)/(max-min)*bins));
2458 while ( (ibin += bins) < 0)
2463 else if (ibin >= bins)
2465 while ( (ibin -= bins) >= bins)
2471 if (ibin >= 0 && ibin < bins)
2473 window->Histo[gUsed][ibin] += 1.;
2476 window->Ntot[gUsed]++;
2480 else if (t > opt->tmax)
2484 printf("time %f larger than tmax %f, stop reading this pullx/pullf file\n", t, opt->tmax);
2496 for (i = 0; i < ny; i++)
2502 //! read pullf-files.dat or pullx-files.dat and tpr-files.dat
2503 static void read_tpr_pullxf_files(char **fnTprs, char **fnPull, int nfiles,
2504 t_UmbrellaHeader* header,
2505 t_UmbrellaWindow *window, t_UmbrellaOptions *opt)
2508 real mintmp, maxtmp;
2510 printf("Reading %d tpr and pullf files\n", nfiles);
2512 /* min and max not given? */
2515 printf("Automatic determination of boundaries...\n");
2518 for (i = 0; i < nfiles; i++)
2520 if (whaminFileType(fnTprs[i]) != whamin_tpr)
2522 gmx_fatal(FARGS, "Expected the %d'th file in input file to be a tpr file\n", i);
2524 read_tpr_header(fnTprs[i], header, opt, (opt->nCoordsel > 0) ? &opt->coordsel[i] : nullptr);
2525 if (whaminFileType(fnPull[i]) != whamin_pullxf)
2527 gmx_fatal(FARGS, "Expected the %d'th file in input file to be a xvg (pullx/pullf) file\n", i);
2529 read_pull_xf(fnPull[i], header, nullptr, opt, TRUE, &mintmp, &maxtmp,
2530 (opt->nCoordsel > 0) ? &opt->coordsel[i] : nullptr);
2531 if (maxtmp > opt->max)
2535 if (mintmp < opt->min)
2540 printf("\nDetermined boundaries to %f and %f\n\n", opt->min, opt->max);
2541 if (opt->bBoundsOnly)
2543 printf("Found option -boundsonly, now exiting.\n");
2547 /* store stepsize in profile */
2548 opt->dz = (opt->max-opt->min)/opt->bins;
2550 bool foundData = false;
2551 for (i = 0; i < nfiles; i++)
2553 if (whaminFileType(fnTprs[i]) != whamin_tpr)
2555 gmx_fatal(FARGS, "Expected the %d'th file in input file to be a tpr file\n", i);
2557 read_tpr_header(fnTprs[i], header, opt, (opt->nCoordsel > 0) ? &opt->coordsel[i] : nullptr);
2558 if (whaminFileType(fnPull[i]) != whamin_pullxf)
2560 gmx_fatal(FARGS, "Expected the %d'th file in input file to be a xvg (pullx/pullf) file\n", i);
2562 read_pull_xf(fnPull[i], header, window+i, opt, FALSE, nullptr, nullptr,
2563 (opt->nCoordsel > 0) ? &opt->coordsel[i] : nullptr);
2564 if (window[i].Ntot[0] == 0)
2566 fprintf(stderr, "\nWARNING, no data points read from file %s (check -b option)\n", fnPull[i]);
2575 gmx_fatal(FARGS, "No data points were found in pullf/pullx files. Maybe you need to specify the -b option?\n");
2578 for (i = 0; i < nfiles; i++)
2587 /*! \brief Read integrated autocorrelation times from input file (option -iiact)
2589 * Note: Here we consider tau[int] := int_0^inf ACF(t) as the integrated autocorrelation times.
2590 * The factor `g := 1 + 2*tau[int]` subsequently enters the uncertainty.
2592 static void readIntegratedAutocorrelationTimes(t_UmbrellaWindow *window, int nwins, const char* fn)
2594 int nlines, ny, i, ig;
2597 printf("Readging Integrated autocorrelation times from %s ...\n", fn);
2598 nlines = read_xvg(fn, &iact, &ny);
2599 if (nlines != nwins)
2601 gmx_fatal(FARGS, "Found %d lines with integrated autocorrelation times in %s.\nExpected %d",
2604 for (i = 0; i < nlines; i++)
2606 if (window[i].nPull != ny)
2608 gmx_fatal(FARGS, "You are providing autocorrelation times with option -iiact and the\n"
2609 "number of pull groups is different in different simulations. That is not\n"
2610 "supported yet. Sorry.\n");
2612 for (ig = 0; ig < window[i].nPull; ig++)
2614 /* compare Kumar et al, J Comp Chem 13, 1011-1021 (1992) */
2615 window[i].g[ig] = 1+2*iact[ig][i]/window[i].dt;
2617 if (iact[ig][i] <= 0.0)
2619 fprintf(stderr, "\nWARNING, IACT = %f (window %d, group %d)\n", iact[ig][i], i, ig);
2626 /*! \brief Smooth autocorreltion times along the reaction coordinate.
2629 * if the ACT is subject to high uncertainty in case if limited sampling. Note
2630 * that -in case of limited sampling- the ACT may be severely underestimated.
2631 * Note: the g=1+2tau are overwritten.
2632 * If opt->bAllowReduceIact==FALSE, the ACTs are never reduced, only increased
2635 static void smoothIact(t_UmbrellaWindow *window, int nwins, t_UmbrellaOptions *opt)
2638 double pos, dpos2, siglim, siglim2, gaufact, invtwosig2, w, weight, tausm;
2640 /* only evaluate within +- 3sigma of the Gausian */
2641 siglim = 3.0*opt->sigSmoothIact;
2642 siglim2 = gmx::square(siglim);
2643 /* pre-factor of Gaussian */
2644 gaufact = 1.0/(std::sqrt(2*M_PI)*opt->sigSmoothIact);
2645 invtwosig2 = 0.5/gmx::square(opt->sigSmoothIact);
2647 for (i = 0; i < nwins; i++)
2649 snew(window[i].tausmooth, window[i].nPull);
2650 for (ig = 0; ig < window[i].nPull; ig++)
2654 pos = window[i].pos[ig];
2655 for (j = 0; j < nwins; j++)
2657 for (jg = 0; jg < window[j].nPull; jg++)
2659 dpos2 = gmx::square(window[j].pos[jg]-pos);
2660 if (dpos2 < siglim2)
2662 w = gaufact*std::exp(-dpos2*invtwosig2);
2664 tausm += w*window[j].tau[jg];
2665 /*printf("Weight %g dpos2=%g pos=%g gaufact=%g invtwosig2=%g\n",
2666 w,dpos2,pos,gaufact,invtwosig2); */
2671 if (opt->bAllowReduceIact || tausm > window[i].tau[ig])
2673 window[i].tausmooth[ig] = tausm;
2677 window[i].tausmooth[ig] = window[i].tau[ig];
2679 window[i].g[ig] = 1+2*tausm/window[i].dt;
2684 //! Stop integrating autoccorelation function when ACF drops under this value
2685 #define WHAM_AC_ZERO_LIMIT 0.05
2687 /*! \brief Try to compute the autocorrelation time for each umbrealla window
2689 static void calcIntegratedAutocorrelationTimes(t_UmbrellaWindow *window, int nwins,
2690 t_UmbrellaOptions *opt, const char *fn, const char *xlabel)
2692 int i, ig, ncorr, ntot, j, k, *count, restart;
2693 real *corr, c0, dt, tmp;
2694 real *ztime, av, tausteps;
2695 FILE *fp, *fpcorr = nullptr;
2699 fpcorr = xvgropen("hist_autocorr.xvg", "Autocorrelation functions of umbrella windows",
2700 "time [ps]", "autocorrelation function", opt->oenv);
2704 for (i = 0; i < nwins; i++)
2706 fprintf(stdout, "\rEstimating integrated autocorrelation times ... [%2.0f%%] ...", 100.*(i+1)/nwins);
2708 ntot = window[i].Ntot[0];
2710 /* using half the maximum time as length of autocorrelation function */
2714 gmx_fatal(FARGS, "Tryig to estimtate autocorrelation time from only %d"
2715 " points. Provide more pull data!", ntot);
2718 /* snew(corrSq,ncorr); */
2721 snew(window[i].tau, window[i].nPull);
2722 restart = gmx::roundToInt(opt->acTrestart/dt);
2728 for (ig = 0; ig < window[i].nPull; ig++)
2730 if (ntot != window[i].Ntot[ig])
2732 gmx_fatal(FARGS, "Encountered different nr of frames in different pull groups.\n"
2733 "That should not happen. (%d and %d)\n", ntot, window[i].Ntot[ig]);
2735 ztime = window[i].ztime[ig];
2737 /* calc autocorrelation function C(t) = < [z(tau)-<z>]*[z(tau+t)-<z>]> */
2738 for (j = 0, av = 0; (j < ntot); j++)
2743 for (k = 0; (k < ncorr); k++)
2748 for (j = 0; (j < ntot); j += restart)
2750 for (k = 0; (k < ncorr) && (j+k < ntot); k++)
2752 tmp = (ztime[j]-av)*(ztime[j+k]-av);
2754 /* corrSq[k] += tmp*tmp; */
2758 /* divide by nr of frames for each time displacement */
2759 for (k = 0; (k < ncorr); k++)
2761 /* count probably = (ncorr-k+(restart-1))/restart; */
2762 corr[k] = corr[k]/count[k];
2763 /* variance of autocorrelation function */
2764 /* corrSq[k]=corrSq[k]/count[k]; */
2766 /* normalize such that corr[0] == 0 */
2768 for (k = 0; (k < ncorr); k++)
2771 /* corrSq[k]*=c0*c0; */
2774 /* write ACFs in verbose mode */
2777 for (k = 0; (k < ncorr); k++)
2779 fprintf(fpcorr, "%g %g\n", k*dt, corr[k]);
2781 fprintf(fpcorr, "%s\n", output_env_get_print_xvgr_codes(opt->oenv) ? "&" : "");
2784 /* esimate integrated correlation time, fitting is too unstable */
2785 tausteps = 0.5*corr[0];
2786 /* consider corr below WHAM_AC_ZERO_LIMIT as noise */
2787 for (j = 1; (j < ncorr) && (corr[j] > WHAM_AC_ZERO_LIMIT); j++)
2789 tausteps += corr[j];
2792 /* g = 1+2*tau, see. Ferrenberg/Swendsen, PRL 63:1195 (1989) or
2793 Kumar et al, eq. 28 ff. */
2794 window[i].tau[ig] = tausteps*dt;
2795 window[i].g[ig] = 1+2*tausteps;
2796 /* printf("win %d, group %d, estimated correlation time = %g ps\n",i,ig,window[i].tau[ig]); */
2807 /* plot IACT along reaction coordinate */
2808 fp = xvgropen(fn, "Integrated autocorrelation times", xlabel, "IACT [ps]", opt->oenv);
2809 if (output_env_get_print_xvgr_codes(opt->oenv))
2811 fprintf(fp, "@ s0 symbol 1\n@ s0 symbol size 0.5\n@ s0 line linestyle 0\n");
2812 fprintf(fp, "# WIN tau(gr1) tau(gr2) ...\n");
2813 for (i = 0; i < nwins; i++)
2815 fprintf(fp, "# %3d ", i);
2816 for (ig = 0; ig < window[i].nPull; ig++)
2818 fprintf(fp, " %11g", window[i].tau[ig]);
2823 for (i = 0; i < nwins; i++)
2825 for (ig = 0; ig < window[i].nPull; ig++)
2827 fprintf(fp, "%8g %8g\n", window[i].pos[ig], window[i].tau[ig]);
2830 if (opt->sigSmoothIact > 0.0)
2832 printf("Smoothing autocorrelation times along reaction coordinate with Gaussian of sig = %g\n",
2833 opt->sigSmoothIact);
2834 /* smooth IACT along reaction coordinate and overwrite g=1+2tau */
2835 smoothIact(window, nwins, opt);
2836 fprintf(fp, "%s\n", output_env_get_print_xvgr_codes(opt->oenv) ? "&" : "");
2837 if (output_env_get_print_xvgr_codes(opt->oenv))
2839 fprintf(fp, "@ s1 symbol 1\n@ s1 symbol size 0.5\n@ s1 line linestyle 0\n");
2840 fprintf(fp, "@ s1 symbol color 2\n");
2842 for (i = 0; i < nwins; i++)
2844 for (ig = 0; ig < window[i].nPull; ig++)
2846 fprintf(fp, "%8g %8g\n", window[i].pos[ig], window[i].tausmooth[ig]);
2851 printf("Wrote %s\n", fn);
2855 * compute average and sigma of each umbrella histogram
2857 static void averageSigma(t_UmbrellaWindow *window, int nwins)
2860 real av, sum2, sig, diff, *ztime, nSamplesIndep;
2862 for (i = 0; i < nwins; i++)
2864 snew(window[i].aver, window[i].nPull);
2865 snew(window[i].sigma, window[i].nPull);
2867 ntot = window[i].Ntot[0];
2868 for (ig = 0; ig < window[i].nPull; ig++)
2870 ztime = window[i].ztime[ig];
2871 for (k = 0, av = 0.; k < ntot; k++)
2876 for (k = 0, sum2 = 0.; k < ntot; k++)
2881 sig = std::sqrt(sum2/ntot);
2882 window[i].aver[ig] = av;
2884 /* Note: This estimate for sigma is biased from the limited sampling.
2885 Correct sigma by n/(n-1) where n = number of independent
2886 samples. Only possible if IACT is known.
2890 nSamplesIndep = window[i].N[ig]/(window[i].tau[ig]/window[i].dt);
2891 window[i].sigma[ig] = sig * nSamplesIndep/(nSamplesIndep-1);
2895 window[i].sigma[ig] = sig;
2897 printf("win %d, aver = %f sig = %f\n", i, av, window[i].sigma[ig]);
2904 * Use histograms to compute average force on pull group.
2906 static void computeAverageForce(t_UmbrellaWindow *window, int nWindows, t_UmbrellaOptions *opt)
2908 int i, j, bins = opt->bins, k;
2909 double dz, min = opt->min, max = opt->max, displAv, temp, distance, ztot, ztot_half, w, weight;
2912 dz = (max-min)/bins;
2913 ztot = opt->max-min;
2916 /* Compute average displacement from histograms */
2917 for (j = 0; j < nWindows; ++j)
2919 snew(window[j].forceAv, window[j].nPull);
2920 for (k = 0; k < window[j].nPull; ++k)
2924 for (i = 0; i < opt->bins; ++i)
2926 temp = (1.0*i+0.5)*dz+min;
2927 distance = temp - window[j].pos[k];
2929 { /* in cyclic wham: */
2930 if (distance > ztot_half) /* |distance| < ztot_half */
2934 else if (distance < -ztot_half)
2939 w = window[j].Histo[k][i]/window[j].g[k];
2940 displAv += w*distance;
2942 /* Are we near min or max? We are getting wrong forces from the histgrams since
2943 the histograms are zero outside [min,max). Therefore, assume that the position
2944 on the other side of the histomgram center is equally likely. */
2947 posmirrored = window[j].pos[k]-distance;
2948 if (posmirrored >= max || posmirrored < min)
2950 displAv += -w*distance;
2957 /* average force from average displacement */
2958 window[j].forceAv[k] = displAv*window[j].k[k];
2959 /* sigma from average square displacement */
2960 /* window[j].sigma [k] = sqrt(displAv2); */
2961 /* printf("Win %d, sigma = %f\n",j,sqrt(displAv2)); */
2967 * Check if the complete reaction coordinate is covered by the histograms
2969 static void checkReactionCoordinateCovered(t_UmbrellaWindow *window, int nwins,
2970 t_UmbrellaOptions *opt)
2972 int i, ig, j, bins = opt->bins;
2974 real avcount = 0, z, relcount, *count;
2975 snew(count, opt->bins);
2977 for (j = 0; j < opt->bins; ++j)
2979 for (i = 0; i < nwins; i++)
2981 for (ig = 0; ig < window[i].nPull; ig++)
2983 count[j] += window[i].Histo[ig][j];
2986 avcount += 1.0*count[j];
2989 for (j = 0; j < bins; ++j)
2991 relcount = count[j]/avcount;
2992 z = (j+0.5)*opt->dz+opt->min;
2993 bBoundary = j<bins/20 || (bins-j)>bins/20;
2994 /* check for bins with no data */
2997 fprintf(stderr, "\nWARNING, no data point in bin %d (z=%g) !\n"
2998 "You may not get a reasonable profile. Check your histograms!\n", j, z);
3000 /* and check for poor sampling */
3001 else if (relcount < 0.005 && !bBoundary)
3003 fprintf(stderr, "Warning, poor sampling bin %d (z=%g). Check your histograms!\n", j, z);
3009 /*! \brief Compute initial potential by integrating the average force
3011 * This speeds up the convergence by roughly a factor of 2
3013 static void guessPotByIntegration(t_UmbrellaWindow *window, int nWindows, t_UmbrellaOptions *opt, const char *xlabel)
3015 int i, j, ig, bins = opt->bins, nHist, winmin, groupmin;
3016 double dz, min = opt->min, *pot, pos, hispos, dist, diff, fAv, distmin, *f;
3019 dz = (opt->max-min)/bins;
3021 printf("Getting initial potential by integration.\n");
3023 /* Compute average displacement from histograms */
3024 computeAverageForce(window, nWindows, opt);
3026 /* Get force for each bin from all histograms in this bin, or, alternatively,
3027 if no histograms are inside this bin, from the closest histogram */
3030 for (j = 0; j < opt->bins; ++j)
3032 pos = (1.0*j+0.5)*dz+min;
3036 groupmin = winmin = 0;
3037 for (i = 0; i < nWindows; i++)
3039 for (ig = 0; ig < window[i].nPull; ig++)
3041 hispos = window[i].pos[ig];
3042 dist = std::abs(hispos-pos);
3043 /* average force within bin */
3047 fAv += window[i].forceAv[ig];
3049 /* at the same time, remember closest histogram */
3058 /* if no histogram found in this bin, use closest histogram */
3065 fAv = window[winmin].forceAv[groupmin];
3069 for (j = 1; j < opt->bins; ++j)
3071 pot[j] = pot[j-1] - 0.5*dz*(f[j-1]+f[j]);
3074 /* cyclic wham: linearly correct possible offset */
3077 diff = (pot[bins-1]-pot[0])/(bins-1);
3078 for (j = 1; j < opt->bins; ++j)
3085 fp = xvgropen("pmfintegrated.xvg", "PMF from force integration", xlabel, "PMF (kJ/mol)", opt->oenv);
3086 for (j = 0; j < opt->bins; ++j)
3088 fprintf(fp, "%g %g\n", (j+0.5)*dz+opt->min, pot[j]);
3091 printf("verbose mode: wrote %s with PMF from interated forces\n", "pmfintegrated.xvg");
3094 /* get initial z=exp(-F[i]/kT) from integrated potential, where F[i] denote the free
3095 energy offsets which are usually determined by wham
3096 First: turn pot into probabilities:
3098 for (j = 0; j < opt->bins; ++j)
3100 pot[j] = std::exp(-pot[j]/(BOLTZ*opt->Temperature));
3102 calc_z(pot, window, nWindows, opt, TRUE);
3108 //! Count number of words in an line
3109 static int wordcount(char *ptr)
3114 if (std::strlen(ptr) == 0)
3118 /* fprintf(stderr,"ptr='%s'\n",ptr); */
3120 for (i = 0; (ptr[i] != '\0'); i++)
3122 is[cur] = isspace(ptr[i]);
3123 if ((i > 0) && (is[cur] && !is[1-cur]))
3132 /*! \brief Read input file for pull group selection (option -is)
3134 * TO DO: ptr=fgets(...) is never freed (small memory leak)
3136 static void readPullCoordSelection(t_UmbrellaOptions *opt, char **fnTpr, int nTpr)
3139 int i, iline, n, len = STRLEN, temp;
3140 char *ptr = nullptr, *tmpbuf = nullptr;
3141 char fmt[1024], fmtign[1024];
3142 int block = 1, sizenow;
3144 fp = gmx_ffopen(opt->fnCoordSel, "r");
3145 opt->coordsel = nullptr;
3150 while ( (ptr = fgets3(fp, tmpbuf, &len)) != nullptr)
3155 if (iline >= sizenow)
3158 srenew(opt->coordsel, sizenow);
3160 opt->coordsel[iline].n = n;
3161 opt->coordsel[iline].nUse = 0;
3162 snew(opt->coordsel[iline].bUse, n);
3165 for (i = 0; i < n; i++)
3167 std::strcpy(fmt, fmtign);
3168 std::strcat(fmt, "%d");
3169 if (sscanf(ptr, fmt, &temp))
3171 opt->coordsel[iline].bUse[i] = (temp > 0);
3172 if (opt->coordsel[iline].bUse[i])
3174 opt->coordsel[iline].nUse++;
3177 std::strcat(fmtign, "%*s");
3181 opt->nCoordsel = iline;
3182 if (nTpr != opt->nCoordsel)
3184 gmx_fatal(FARGS, "Found %d tpr files but %d lines in %s\n", nTpr, opt->nCoordsel,
3188 printf("\nUse only these pull coordinates:\n");
3189 for (iline = 0; iline < nTpr; iline++)
3191 printf("%s (%d of %d coordinates):", fnTpr[iline], opt->coordsel[iline].nUse, opt->coordsel[iline].n);
3192 for (i = 0; i < opt->coordsel[iline].n; i++)
3194 if (opt->coordsel[iline].bUse[i])
3207 #define WHAMBOOLXOR(a, b) ( ((!(a)) && (b)) || ((a) && (!(b))))
3209 //! Number of elements in fnm (used for command line parsing)
3210 #define NFILE asize(fnm)
3212 //! The main gmx wham routine
3213 int gmx_wham(int argc, char *argv[])
3215 const char *desc[] = {
3216 "[THISMODULE] is an analysis program that implements the Weighted",
3217 "Histogram Analysis Method (WHAM). It is intended to analyze",
3218 "output files generated by umbrella sampling simulations to ",
3219 "compute a potential of mean force (PMF).[PAR]",
3221 "[THISMODULE] is currently not fully up to date. It only supports pull setups",
3222 "where the first pull coordinate(s) is/are umbrella pull coordinates",
3223 "and, if multiple coordinates need to be analyzed, all used the same",
3224 "geometry and dimensions. In most cases this is not an issue.[PAR]",
3225 "At present, three input modes are supported.",
3227 "* With option [TT]-it[tt], the user provides a file which contains the",
3228 " file names of the umbrella simulation run-input files ([REF].tpr[ref] files),",
3229 " AND, with option [TT]-ix[tt], a file which contains file names of",
3230 " the pullx [TT]mdrun[tt] output files. The [REF].tpr[ref] and pullx files must",
3231 " be in corresponding order, i.e. the first [REF].tpr[ref] created the",
3232 " first pullx, etc.",
3233 "* Same as the previous input mode, except that the the user",
3234 " provides the pull force output file names ([TT]pullf.xvg[tt]) with option [TT]-if[tt].",
3235 " From the pull force the position in the umbrella potential is",
3236 " computed. This does not work with tabulated umbrella potentials.",
3237 "* With option [TT]-ip[tt], the user provides file names of (gzipped) [REF].pdo[ref] files, i.e.",
3238 " the GROMACS 3.3 umbrella output files. If you have some unusual",
3239 " reaction coordinate you may also generate your own [REF].pdo[ref] files and",
3240 " feed them with the [TT]-ip[tt] option into to [THISMODULE]. The [REF].pdo[ref] file header",
3241 " must be similar to the following::",
3244 " # Component selection: 0 0 1",
3246 " # Ref. Group 'TestAtom'",
3247 " # Nr. of pull groups 2",
3248 " # Group 1 'GR1' Umb. Pos. 5.0 Umb. Cons. 1000.0",
3249 " # Group 2 'GR2' Umb. Pos. 2.0 Umb. Cons. 500.0",
3252 " The number of pull groups, umbrella positions, force constants, and names ",
3253 " may (of course) differ. Following the header, a time column and ",
3254 " a data column for each pull group follows (i.e. the displacement",
3255 " with respect to the umbrella center). Up to four pull groups are possible ",
3256 " per [REF].pdo[ref] file at present.[PAR]",
3257 "By default, all pull coordinates found in all pullx/pullf files are used in WHAM. If only ",
3258 "some of the pull coordinates should be used, a pull coordinate selection file (option [TT]-is[tt]) can ",
3259 "be provided. The selection file must contain one line for each tpr file in tpr-files.dat.",
3260 "Each of these lines must contain one digit (0 or 1) for each pull coordinate in the tpr file. ",
3261 "Here, 1 indicates that the pull coordinate is used in WHAM, and 0 means it is omitted. Example:",
3262 "If you have three tpr files, each containing 4 pull coordinates, but only pull coordinates 1 and 2 should be ",
3263 "used, coordsel.dat looks like this::",
3269 "By default, the output files are::",
3271 " [TT]-o[tt] PMF output file",
3272 " [TT]-hist[tt] Histograms output file",
3274 "Always check whether the histograms sufficiently overlap.[PAR]",
3275 "The umbrella potential is assumed to be harmonic and the force constants are ",
3276 "read from the [REF].tpr[ref] or [REF].pdo[ref] files. If a non-harmonic umbrella force was applied ",
3277 "a tabulated potential can be provided with [TT]-tab[tt].",
3282 "* [TT]-bins[tt] Number of bins used in analysis",
3283 "* [TT]-temp[tt] Temperature in the simulations",
3284 "* [TT]-tol[tt] Stop iteration if profile (probability) changed less than tolerance",
3285 "* [TT]-auto[tt] Automatic determination of boundaries",
3286 "* [TT]-min,-max[tt] Boundaries of the profile",
3288 "The data points that are used to compute the profile",
3289 "can be restricted with options [TT]-b[tt], [TT]-e[tt], and [TT]-dt[tt]. ",
3290 "Adjust [TT]-b[tt] to ensure sufficient equilibration in each ",
3291 "umbrella window.[PAR]",
3292 "With [TT]-log[tt] (default) the profile is written in energy units, otherwise ",
3293 "(with [TT]-nolog[tt]) as probability. The unit can be specified with [TT]-unit[tt]. ",
3294 "With energy output, the energy in the first bin is defined to be zero. ",
3295 "If you want the free energy at a different ",
3296 "position to be zero, set [TT]-zprof0[tt] (useful with bootstrapping, see below).[PAR]",
3297 "For cyclic or periodic reaction coordinates (dihedral angle, channel PMF",
3298 "without osmotic gradient), the option [TT]-cycl[tt] is useful.",
3299 "[THISMODULE] will make use of the",
3300 "periodicity of the system and generate a periodic PMF. The first and the last bin of the",
3301 "reaction coordinate will assumed be be neighbors.[PAR]",
3302 "Option [TT]-sym[tt] symmetrizes the profile around z=0 before output, ",
3303 "which may be useful for, e.g. membranes.",
3308 "If available, the number of OpenMP threads used by gmx wham can be controlled by setting",
3309 "the [TT]OMP_NUM_THREADS[tt] environment variable.",
3314 "With [TT]-ac[tt], [THISMODULE] estimates the integrated autocorrelation ",
3315 "time (IACT) [GRK]tau[grk] for each umbrella window and weights the respective ",
3316 "window with 1/[1+2*[GRK]tau[grk]/dt]. The IACTs are written ",
3317 "to the file defined with [TT]-oiact[tt]. In verbose mode, all ",
3318 "autocorrelation functions (ACFs) are written to [TT]hist_autocorr.xvg[tt]. ",
3319 "Because the IACTs can be severely underestimated in case of limited ",
3320 "sampling, option [TT]-acsig[tt] allows one to smooth the IACTs along the ",
3321 "reaction coordinate with a Gaussian ([GRK]sigma[grk] provided with [TT]-acsig[tt], ",
3322 "see output in [TT]iact.xvg[tt]). Note that the IACTs are estimated by simple ",
3323 "integration of the ACFs while the ACFs are larger 0.05.",
3324 "If you prefer to compute the IACTs by a more sophisticated (but possibly ",
3325 "less robust) method such as fitting to a double exponential, you can ",
3326 "compute the IACTs with [gmx-analyze] and provide them to [THISMODULE] with the file ",
3327 "[TT]iact-in.dat[tt] (option [TT]-iiact[tt]), which should contain one line per ",
3328 "input file ([REF].pdo[ref] or pullx/f file) and one column per pull coordinate in the respective file.",
3333 "Statistical errors may be estimated with bootstrap analysis. Use it with care, ",
3334 "otherwise the statistical error may be substantially underestimated. ",
3335 "More background and examples for the bootstrap technique can be found in ",
3336 "Hub, de Groot and Van der Spoel, JCTC (2010) 6: 3713-3720.",
3337 "[TT]-nBootstrap[tt] defines the number of bootstraps (use, e.g., 100). ",
3338 "Four bootstrapping methods are supported and ",
3339 "selected with [TT]-bs-method[tt].",
3341 "* [TT]b-hist[tt] Default: complete histograms are considered as independent ",
3342 " data points, and the bootstrap is carried out by assigning random weights to the ",
3343 " histograms (\"Bayesian bootstrap\"). Note that each point along the reaction coordinate",
3344 " must be covered by multiple independent histograms (e.g. 10 histograms), otherwise the ",
3345 " statistical error is underestimated.",
3346 "* [TT]hist[tt] Complete histograms are considered as independent data points. ",
3347 " For each bootstrap, N histograms are randomly chosen from the N given histograms ",
3348 " (allowing duplication, i.e. sampling with replacement).",
3349 " To avoid gaps without data along the reaction coordinate blocks of histograms ",
3350 " ([TT]-histbs-block[tt]) may be defined. In that case, the given histograms are ",
3351 " divided into blocks and only histograms within each block are mixed. Note that ",
3352 " the histograms within each block must be representative for all possible histograms, ",
3353 " otherwise the statistical error is underestimated.",
3354 "* [TT]traj[tt] The given histograms are used to generate new random trajectories,",
3355 " such that the generated data points are distributed according the given histograms ",
3356 " and properly autocorrelated. The autocorrelation time (ACT) for each window must be ",
3357 " known, so use [TT]-ac[tt] or provide the ACT with [TT]-iiact[tt]. If the ACT of all ",
3358 " windows are identical (and known), you can also provide them with [TT]-bs-tau[tt]. ",
3359 " Note that this method may severely underestimate the error in case of limited sampling, ",
3360 " that is if individual histograms do not represent the complete phase space at ",
3361 " the respective positions.",
3362 "* [TT]traj-gauss[tt] The same as method [TT]traj[tt], but the trajectories are ",
3363 " not bootstrapped from the umbrella histograms but from Gaussians with the average ",
3364 " and width of the umbrella histograms. That method yields similar error estimates ",
3365 " like method [TT]traj[tt].",
3367 "Bootstrapping output:",
3369 "* [TT]-bsres[tt] Average profile and standard deviations",
3370 "* [TT]-bsprof[tt] All bootstrapping profiles",
3372 "With [TT]-vbs[tt] (verbose bootstrapping), the histograms of each bootstrap are written, ",
3373 "and, with bootstrap method [TT]traj[tt], the cumulative distribution functions of ",
3377 const char *en_unit[] = {nullptr, "kJ", "kCal", "kT", nullptr};
3378 const char *en_unit_label[] = {"", "E (kJ mol\\S-1\\N)", "E (kcal mol\\S-1\\N)", "E (kT)", nullptr};
3379 const char *en_bsMethod[] = { nullptr, "b-hist", "hist", "traj", "traj-gauss", nullptr };
3380 static t_UmbrellaOptions opt;
3383 { "-min", FALSE, etREAL, {&opt.min},
3384 "Minimum coordinate in profile"},
3385 { "-max", FALSE, etREAL, {&opt.max},
3386 "Maximum coordinate in profile"},
3387 { "-auto", FALSE, etBOOL, {&opt.bAuto},
3388 "Determine min and max automatically"},
3389 { "-bins", FALSE, etINT, {&opt.bins},
3390 "Number of bins in profile"},
3391 { "-temp", FALSE, etREAL, {&opt.Temperature},
3393 { "-tol", FALSE, etREAL, {&opt.Tolerance},
3395 { "-v", FALSE, etBOOL, {&opt.verbose},
3397 { "-b", FALSE, etREAL, {&opt.tmin},
3398 "First time to analyse (ps)"},
3399 { "-e", FALSE, etREAL, {&opt.tmax},
3400 "Last time to analyse (ps)"},
3401 { "-dt", FALSE, etREAL, {&opt.dt},
3402 "Analyse only every dt ps"},
3403 { "-histonly", FALSE, etBOOL, {&opt.bHistOnly},
3404 "Write histograms and exit"},
3405 { "-boundsonly", FALSE, etBOOL, {&opt.bBoundsOnly},
3406 "Determine min and max and exit (with [TT]-auto[tt])"},
3407 { "-log", FALSE, etBOOL, {&opt.bLog},
3408 "Calculate the log of the profile before printing"},
3409 { "-unit", FALSE, etENUM, {en_unit},
3410 "Energy unit in case of log output" },
3411 { "-zprof0", FALSE, etREAL, {&opt.zProf0},
3412 "Define profile to 0.0 at this position (with [TT]-log[tt])"},
3413 { "-cycl", FALSE, etBOOL, {&opt.bCycl},
3414 "Create cyclic/periodic profile. Assumes min and max are the same point."},
3415 { "-sym", FALSE, etBOOL, {&opt.bSym},
3416 "Symmetrize profile around z=0"},
3417 { "-hist-eq", FALSE, etBOOL, {&opt.bHistEq},
3418 "HIDDENEnforce equal weight for all histograms. (Non-Weighed-HAM)"},
3419 { "-ac", FALSE, etBOOL, {&opt.bCalcTauInt},
3420 "Calculate integrated autocorrelation times and use in wham"},
3421 { "-acsig", FALSE, etREAL, {&opt.sigSmoothIact},
3422 "Smooth autocorrelation times along reaction coordinate with Gaussian of this [GRK]sigma[grk]"},
3423 { "-ac-trestart", FALSE, etREAL, {&opt.acTrestart},
3424 "When computing autocorrelation functions, restart computing every .. (ps)"},
3425 { "-acred", FALSE, etBOOL, {&opt.bAllowReduceIact},
3426 "HIDDENWhen smoothing the ACTs, allows one to reduce ACTs. Otherwise, only increase ACTs "
3427 "during smoothing"},
3428 { "-nBootstrap", FALSE, etINT, {&opt.nBootStrap},
3429 "nr of bootstraps to estimate statistical uncertainty (e.g., 200)" },
3430 { "-bs-method", FALSE, etENUM, {en_bsMethod},
3431 "Bootstrap method" },
3432 { "-bs-tau", FALSE, etREAL, {&opt.tauBootStrap},
3433 "Autocorrelation time (ACT) assumed for all histograms. Use option [TT]-ac[tt] if ACT is unknown."},
3434 { "-bs-seed", FALSE, etINT, {&opt.bsSeed},
3435 "Seed for bootstrapping. (-1 = use time)"},
3436 { "-histbs-block", FALSE, etINT, {&opt.histBootStrapBlockLength},
3437 "When mixing histograms only mix within blocks of [TT]-histbs-block[tt]."},
3438 { "-vbs", FALSE, etBOOL, {&opt.bs_verbose},
3439 "Verbose bootstrapping. Print the CDFs and a histogram file for each bootstrap."},
3440 { "-stepout", FALSE, etINT, {&opt.stepchange},
3441 "HIDDENWrite maximum change every ... (set to 1 with [TT]-v[tt])"},
3442 { "-updateContr", FALSE, etINT, {&opt.stepUpdateContrib},
3443 "HIDDENUpdate table with significan contributions to WHAM every ... iterations"},
3447 { efDAT, "-ix", "pullx-files", ffOPTRD}, /* wham input: pullf.xvg's and tprs */
3448 { efDAT, "-if", "pullf-files", ffOPTRD}, /* wham input: pullf.xvg's and tprs */
3449 { efDAT, "-it", "tpr-files", ffOPTRD}, /* wham input: tprs */
3450 { efDAT, "-ip", "pdo-files", ffOPTRD}, /* wham input: pdo files (gmx3 style) */
3451 { efDAT, "-is", "coordsel", ffOPTRD}, /* input: select pull coords to use */
3452 { efXVG, "-o", "profile", ffWRITE }, /* output file for profile */
3453 { efXVG, "-hist", "histo", ffWRITE}, /* output file for histograms */
3454 { efXVG, "-oiact", "iact", ffOPTWR}, /* writing integrated autocorrelation times */
3455 { efDAT, "-iiact", "iact-in", ffOPTRD}, /* reading integrated autocorrelation times */
3456 { efXVG, "-bsres", "bsResult", ffOPTWR}, /* average and errors of bootstrap analysis */
3457 { efXVG, "-bsprof", "bsProfs", ffOPTWR}, /* output file for bootstrap profiles */
3458 { efDAT, "-tab", "umb-pot", ffOPTRD}, /* Tabulated umbrella potential (if not harmonic) */
3461 int i, j, l, nfiles, nwins, nfiles2;
3462 t_UmbrellaHeader header;
3463 t_UmbrellaWindow * window = nullptr;
3464 double *profile, maxchange = 1e20;
3465 gmx_bool bMinSet, bMaxSet, bAutoSet, bExact = FALSE;
3466 char **fninTpr, **fninPull, **fninPdo;
3468 FILE *histout, *profout;
3469 char xlabel[STRLEN], ylabel[256], title[256];
3472 opt.verbose = FALSE;
3473 opt.bHistOnly = FALSE;
3482 opt.coordsel = nullptr;
3484 /* bootstrapping stuff */
3486 opt.bsMethod = bsMethod_hist;
3487 opt.tauBootStrap = 0.0;
3489 opt.histBootStrapBlockLength = 8;
3490 opt.bs_verbose = FALSE;
3495 opt.Temperature = 298;
3496 opt.Tolerance = 1e-6;
3497 opt.bBoundsOnly = FALSE;
3499 opt.bCalcTauInt = FALSE;
3500 opt.sigSmoothIact = 0.0;
3501 opt.bAllowReduceIact = TRUE;
3502 opt.bInitPotByIntegration = TRUE;
3503 opt.acTrestart = 1.0;
3504 opt.stepchange = 100;
3505 opt.stepUpdateContrib = 100;
3507 if (!parse_common_args(&argc, argv, 0,
3508 NFILE, fnm, asize(pa), pa, asize(desc), desc, 0, nullptr, &opt.oenv))
3513 opt.unit = nenum(en_unit);
3514 opt.bsMethod = nenum(en_bsMethod);
3516 opt.bProf0Set = opt2parg_bSet("-zprof0", asize(pa), pa);
3518 opt.bTab = opt2bSet("-tab", NFILE, fnm);
3519 opt.bPdo = opt2bSet("-ip", NFILE, fnm);
3520 opt.bTpr = opt2bSet("-it", NFILE, fnm);
3521 opt.bPullx = opt2bSet("-ix", NFILE, fnm);
3522 opt.bPullf = opt2bSet("-if", NFILE, fnm);
3523 opt.bTauIntGiven = opt2bSet("-iiact", NFILE, fnm);
3524 if (opt.bTab && opt.bPullf)
3526 gmx_fatal(FARGS, "Force input does not work with tabulated potentials. "
3527 "Provide pullx.xvg or pdo files!");
3530 if (!opt.bPdo && !WHAMBOOLXOR(opt.bPullx, opt.bPullf))
3532 gmx_fatal(FARGS, "Give either pullx (-ix) OR pullf (-if) data. Not both.");
3534 if (!opt.bPdo && !(opt.bTpr || opt.bPullf || opt.bPullx))
3536 gmx_fatal(FARGS, "gmx wham supports three input modes, pullx, pullf, or pdo file input."
3537 "\n\n Check gmx wham -h !");
3540 opt.fnPdo = opt2fn("-ip", NFILE, fnm);
3541 opt.fnTpr = opt2fn("-it", NFILE, fnm);
3542 opt.fnPullf = opt2fn("-if", NFILE, fnm);
3543 opt.fnPullx = opt2fn("-ix", NFILE, fnm);
3544 opt.fnCoordSel = opt2fn_null("-is", NFILE, fnm);
3546 bMinSet = opt2parg_bSet("-min", asize(pa), pa);
3547 bMaxSet = opt2parg_bSet("-max", asize(pa), pa);
3548 bAutoSet = opt2parg_bSet("-auto", asize(pa), pa);
3549 if ( (bMinSet || bMaxSet) && bAutoSet)
3551 gmx_fatal(FARGS, "With -auto, do not give -min or -max\n");
3554 if ( (bMinSet && !bMaxSet) || (!bMinSet && bMaxSet))
3556 gmx_fatal(FARGS, "When giving -min, you must give -max (and vice versa), too\n");
3559 if (bMinSet && opt.bAuto)
3561 printf("Note: min and max given, switching off -auto.\n");
3565 if (opt.bTauIntGiven && opt.bCalcTauInt)
3567 gmx_fatal(FARGS, "Either read (option -iiact) or calculate (option -ac) the\n"
3568 "the autocorrelation times. Not both.");
3571 if (opt.tauBootStrap > 0.0 && opt2parg_bSet("-ac", asize(pa), pa))
3573 gmx_fatal(FARGS, "Either compute autocorrelation times (ACTs) (option -ac) or "
3574 "provide it with -bs-tau for bootstrapping. Not Both.\n");
3576 if (opt.tauBootStrap > 0.0 && opt2bSet("-iiact", NFILE, fnm))
3578 gmx_fatal(FARGS, "Either provide autocorrelation times (ACTs) with file iact-in.dat "
3579 "(option -iiact) or define all ACTs with -bs-tau for bootstrapping\n. Not Both.");
3582 /* Reading gmx4/gmx5 pull output and tpr files */
3583 if (opt.bTpr || opt.bPullf || opt.bPullx)
3585 read_wham_in(opt.fnTpr, &fninTpr, &nfiles, &opt);
3587 fnPull = opt.bPullf ? opt.fnPullf : opt.fnPullx;
3588 read_wham_in(fnPull, &fninPull, &nfiles2, &opt);
3589 printf("Found %d tpr and %d pull %s files in %s and %s, respectively\n",
3590 nfiles, nfiles2, opt.bPullf ? "force" : "position", opt.fnTpr, fnPull);
3591 if (nfiles != nfiles2)
3593 gmx_fatal(FARGS, "Found %d file names in %s, but %d in %s\n", nfiles,
3594 opt.fnTpr, nfiles2, fnPull);
3597 /* Read file that selects the pull group to be used */
3598 if (opt.fnCoordSel != nullptr)
3600 readPullCoordSelection(&opt, fninTpr, nfiles);
3603 window = initUmbrellaWindows(nfiles);
3604 read_tpr_pullxf_files(fninTpr, fninPull, nfiles, &header, window, &opt);
3607 { /* reading pdo files */
3608 if (opt.fnCoordSel != nullptr)
3610 gmx_fatal(FARGS, "Reading a -is file is not supported with PDO input files.\n"
3611 "Use awk or a similar tool to pick the required pull groups from your PDO files\n");
3613 read_wham_in(opt.fnPdo, &fninPdo, &nfiles, &opt);
3614 printf("Found %d pdo files in %s\n", nfiles, opt.fnPdo);
3615 window = initUmbrellaWindows(nfiles);
3616 read_pdo_files(fninPdo, nfiles, &header, window, &opt);
3619 /* It is currently assumed that all pull coordinates have the same geometry, so they also have the same coordinate units.
3620 We can therefore get the units for the xlabel from the first coordinate. */
3621 sprintf(xlabel, "\\xx\\f{} (%s)", header.pcrd[0].coord_unit);
3625 /* enforce equal weight for all histograms? */
3628 enforceEqualWeights(window, nwins);
3631 /* write histograms */
3632 histout = xvgropen(opt2fn("-hist", NFILE, fnm), "Umbrella histograms",
3633 xlabel, "count", opt.oenv);
3634 for (l = 0; l < opt.bins; ++l)
3636 fprintf(histout, "%e\t", (l+0.5)/opt.bins*(opt.max-opt.min)+opt.min);
3637 for (i = 0; i < nwins; ++i)
3639 for (j = 0; j < window[i].nPull; ++j)
3641 fprintf(histout, "%e\t", window[i].Histo[j][l]);
3644 fprintf(histout, "\n");
3647 printf("Wrote %s\n", opt2fn("-hist", NFILE, fnm));
3650 printf("Wrote histograms to %s, now exiting.\n", opt2fn("-hist", NFILE, fnm));
3654 /* Using tabulated umbrella potential */
3657 setup_tab(opt2fn("-tab", NFILE, fnm), &opt);
3660 /* Integrated autocorrelation times provided ? */
3661 if (opt.bTauIntGiven)
3663 readIntegratedAutocorrelationTimes(window, nwins, opt2fn("-iiact", NFILE, fnm));
3666 /* Compute integrated autocorrelation times */
3667 if (opt.bCalcTauInt)
3669 calcIntegratedAutocorrelationTimes(window, nwins, &opt, opt2fn("-oiact", NFILE, fnm), xlabel);
3672 /* calc average and sigma for each histogram
3673 (maybe required for bootstrapping. If not, this is fast anyhow) */
3674 if (opt.nBootStrap && opt.bsMethod == bsMethod_trajGauss)
3676 averageSigma(window, nwins);
3679 /* Get initial potential by simple integration */
3680 if (opt.bInitPotByIntegration)
3682 guessPotByIntegration(window, nwins, &opt, xlabel);
3685 /* Check if complete reaction coordinate is covered */
3686 checkReactionCoordinateCovered(window, nwins, &opt);
3688 /* Calculate profile */
3689 snew(profile, opt.bins);
3697 if ( (i%opt.stepUpdateContrib) == 0)
3699 setup_acc_wham(profile, window, nwins, &opt);
3701 if (maxchange < opt.Tolerance)
3704 /* if (opt.verbose) */
3705 printf("Switched to exact iteration in iteration %d\n", i);
3707 calc_profile(profile, window, nwins, &opt, bExact);
3708 if (((i%opt.stepchange) == 0 || i == 1) && i != 0)
3710 printf("\t%4d) Maximum change %e\n", i, maxchange);
3714 while ( (maxchange = calc_z(profile, window, nwins, &opt, bExact)) > opt.Tolerance || !bExact);
3715 printf("Converged in %d iterations. Final maximum change %g\n", i, maxchange);
3717 /* calc error from Kumar's formula */
3718 /* Unclear how the error propagates along reaction coordinate, therefore
3720 /* calc_error_kumar(profile,window, nwins,&opt); */
3722 /* Write profile in energy units? */
3725 prof_normalization_and_unit(profile, &opt);
3726 std::strcpy(ylabel, en_unit_label[opt.unit]);
3727 std::strcpy(title, "Umbrella potential");
3731 std::strcpy(ylabel, "Density of states");
3732 std::strcpy(title, "Density of states");
3735 /* symmetrize profile around z=0? */
3738 symmetrizeProfile(profile, &opt);
3741 /* write profile or density of states */
3742 profout = xvgropen(opt2fn("-o", NFILE, fnm), title, xlabel, ylabel, opt.oenv);
3743 for (i = 0; i < opt.bins; ++i)
3745 fprintf(profout, "%e\t%e\n", (i+0.5)/opt.bins*(opt.max-opt.min)+opt.min, profile[i]);
3748 printf("Wrote %s\n", opt2fn("-o", NFILE, fnm));
3750 /* Bootstrap Method */
3753 do_bootstrapping(opt2fn("-bsres", NFILE, fnm), opt2fn("-bsprof", NFILE, fnm),
3754 opt2fn("-hist", NFILE, fnm),
3755 xlabel, ylabel, profile, window, nwins, &opt);
3759 freeUmbrellaWindows(window, nfiles);
3761 printf("\nIn case you use results from gmx wham for a publication, please cite:\n");
3762 please_cite(stdout, "Hub2010");